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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00611455
Registration number
NCT00611455
Ethics application status
Date submitted
16/01/2008
Date registered
11/02/2008
Date last updated
6/11/2017
Titles & IDs
Public title
Investigating Clinical Efficacy of Ofatumumab in Adult Rheumatoid Arthritis (RA) Patients Who Had an Inadequate Response to MTX Therapy
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Scientific title
A Double-blind, Randomized, Placebo Controlled, Parallel Group, Multi-center, Phase III Trial of Ofatumumab Investigating Clinical Efficacy in Adult Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
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Secondary ID [1]
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GEN410
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Secondary ID [2]
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110635
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid
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Condition category
Condition code
Musculoskeletal
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Osteoarthritis
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Inflammatory and Immune System
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Rheumatoid arthritis
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - ofatumumab
Treatment: Drugs - Placebo
Experimental: ofatumumab - 1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two 700mg IV infusions taken 14 days apart. A total of 8 infusions cycles given over a 144 week period
Placebo Comparator: 1000 ml Saline - 1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two IV infusions taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period
Treatment: Drugs: ofatumumab
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two 700mg IV infusions taken 14 days apart. A total of 8 infusions cycles given over a 144 week period
Treatment: Drugs: Placebo
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two IV infusions taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24
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Assessment method [1]
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The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced >=20% improvement from baseline in TJC and SJC and a >=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
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Timepoint [1]
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Baseline and Week 24
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Secondary outcome [1]
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Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Weeks 4, 8, 12, 16, and 20
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Assessment method [1]
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The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced >=20% improvement from baseline in TJC and SJC and a >=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
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Timepoint [1]
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Baseline and Weeks 4, 8, 12, 16, and 20
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Secondary outcome [2]
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Number of Participants With a 50% Improvement From Baseline in Their ACR Score (ACR50) at Weeks 4, 8, 12, 16, 20, and 24
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Assessment method [2]
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The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR50 if he experienced >=50% improvement from baseline in TJC and SJC and a >=50% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
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Timepoint [2]
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Baseline and Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [3]
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Number of Participants With a 70% Improvement From Baseline in Their ACR Score (ACR70) at Weeks 4, 8, 12, 16, 20, and 24
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Assessment method [3]
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The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR70 if he experienced >=70% improvement from baseline in TJC and SJC and a >=70% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.
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Timepoint [3]
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Baseline and Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [4]
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Median ACRn at Weeks 4, 8, 12, 16, 20, and 24
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Assessment method [4]
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ACRn = the largest integer n for which a participant (par.) met the criteria requiring an improvement of n%. ACRn is a measure characterizing percent (%) improvement from baseline (IFBL). A par. with an ACRn of X had an improvement of >=X% in tender/swollen joints (TJC/SJC), and an improvement of >=X% in 3 of the 5 parameters (patient [pt] pain assessment, pt global assessment [GA], physician GA, pt self-assessed disability, acute phase reactant). ACRn = minimum(TJC % IFBL, SJC % IFBL, composite measure % IFBL). Composite measure % IFBL is the 3rd highest value of % IFBL for the 5 parameters.
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Timepoint [4]
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Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [5]
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Mean Disease Activity Score Based on 28 Joints (DAS28) at Weeks 4, 8, 12, 16, 20, and 24 Using C-reactive Protein (CRP) as the Acute Phase Reactant (APR)
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Assessment method [5]
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The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of DA can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation.
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Timepoint [5]
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Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [6]
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Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant
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Assessment method [6]
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The DAS28 is a clinical index of RA disease activity that combines information from swollen joints, tender joints, the acute phase reactant, and general health (patient global assessment). Change from baseline in DAS28 is calculated as the Week 4, 8, 12, 16, 20, and 24 values minus the baseline value.
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Timepoint [6]
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Baseline and Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [7]
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Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant
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Assessment method [7]
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The DAS28 is a clinical index of rheumatoid arthritis disease activity (DA) that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of DA can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. APRs are a class of proteins that are useful markers for inflammation.
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Timepoint [7]
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Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [8]
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Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant
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Assessment method [8]
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The DAS28 is a clinical index of RA disease activity that combines information from swollen joints, tender joints, the acute phase reactant, and general health (patient global assessment). Change from baseline in DAS28 is calculated as the Week 4, 8, 12, 16, 20, and 24 values minus the baseline value.
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Timepoint [8]
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Baseline and Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [9]
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Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant
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Assessment method [9]
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The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 <=3.2; moderate responders: change from baseline >1.2 with DAS28 <=3.2 to >5.1 or change from baseline >0.6 to <=1.2 with DAS28 <=3.2 to <=5.1); non-responders: change from baseline <=0.6 or change from baseline >0.6 and <=1.2 with DAS28 >5.1.
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Timepoint [9]
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Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [10]
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Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant
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Assessment method [10]
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The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline >1.2 with DAS28 <=3.2; moderate responders: change from baseline >1.2 with DAS28 <=3.2 to >5.1 or change from baseline >0.6 to <=1.2 with DAS28 <=3.2 to <=5.1); non-responders: change from baseline <=0.6 or change from baseline >0.6 and <=1.2 with DAS28 >5.1.
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Timepoint [10]
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Weeks 4, 8, 12, 16, 20, and 24
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Secondary outcome [11]
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Number of Participants Classified as Responders at Week 24 According to the Self-Assessed Health Assessment Questionnaire Disability Index (HAQ-DI)
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Assessment method [11]
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The HAQ-DI is a 20-question instrument used to assess the degree of difficulty a participant had in accomplishing tasks in 8 functional areas (FAs): dressing, arising, eating, walking, hygiene, reaching, gripping, and errands/chores. Responses for each FA were scored from 0 (no difficulty) to 3 (inability to perform a task). The total score (range of 0-3) was calculated by adding the 8 individual FA scores, then dividing this sum by the total number of components answered. Responders were defined as participants achieving an improvement from baseline in the HAQ-DI score at Week 24 of >=0.22.
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Timepoint [11]
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Week 24
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Secondary outcome [12]
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Number of Participants With Clinical Remission at Week 24
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Assessment method [12]
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Participants achieving clinical remission were defined as those with a low disease activity, i.e., DAS28 score (using CRP) <2.6 at Week 24.
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Timepoint [12]
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Week 24
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Secondary outcome [13]
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Change From Baseline in Tender Joint Count at Week 24
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Assessment method [13]
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Change from baseline in tender joint count was calculated as the Week 24 count minus the baseline count. A total of 68 joints were assessed. Joints were classified as either tender or not tender by an independent assessor, who had documented experience in performing joint assessments.
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Timepoint [13]
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Baseline and Week 24
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Secondary outcome [14]
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Change From Baseline in Swollen Joint Count at Week 24
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Assessment method [14]
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Change from baseline in swollen joint count was calculated as the Week 24 count minus the baseline count. A total of 66 joints were assessed. Joints were classified as either swollen or not swollen by an independent assessor, who had documented experience in performing joint assessments.
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Timepoint [14]
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Baseline and Week 24
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Secondary outcome [15]
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Change From Baseline in the Participant-assessed Pain Score at Week 24
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Assessment method [15]
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A horizontal VAS of 100 mm was used to report the participant's level of joint pain. The scale ranged from 0 (no pain) to 100 (unbearable pain). Participants were instructed to draw a vertical line through the horizontal line to indicate how much joint pain they had. The distance from the "no pain" end to the vertical line drawn by the participant was the joint pain score. Change from baseline was calculated as the Week 24 value minus the baseline value.
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Timepoint [15]
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Baseline and Week 24
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Secondary outcome [16]
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Change From Baseline in Participant-assessed Global Disease Score at Week 24
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Assessment method [16]
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The participant used a horizontal VAS of 100 mm for overall assessment of disease. The scale ranged from 0 (very well) to 100 (very poor). Participants were instructed to draw a vertical line through the horizontal line to indicate the state of the arthritis. The distance from the "very well" end to the vertical line drawn by the participant was the global disease assessment score. Change from baseline in participant-assessed global disease was calculated as the Week 24 value minus the baseline value.
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Timepoint [16]
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Baseline and Week 24
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Secondary outcome [17]
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Change From Baseline in the Physician-assessed Global Disease Score at Week 24
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Assessment method [17]
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The physician used a horizontal VAS of 100 mm for overall assessment of disease. The scale ranged from 0 (very well) to 100 (very poor). Physicians were instructed to draw a vertical line through the horizontal line to indicate the state of the arthritis. The distance from the "very well" end to the vertical line drawn by the participant was the global disease assessment score. Change from baseline in the physician-assessed global disease was calculated as the Week 24 value minus the baseline value.
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Timepoint [17]
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Baseline and Week 24
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Secondary outcome [18]
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Change From Baseline in HAQ-DI Score at Week 24
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Assessment method [18]
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The self-assessed HAQ-DI is a 20-question instrument used to assess the degree of difficulty a participant had in accomplishing tasks in 8 functional areas (FAs): dressing, arising, eating, walking, hygiene, reaching, gripping, and errands/chores. Responses for each FA were scored from 0 (no difficulty) to 3 (inability to perform a task). The total score (range of 0-3) was calculated by adding the 8 individual FA scores, then dividing this sum by the total number of components answered. Change from baseline was calculated as the value at Week 24 minus the baseline value.
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Timepoint [18]
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Baseline and Week 24
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Secondary outcome [19]
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Change From Baseline in CRP at Week 24
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Assessment method [19]
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Blood samples for the determination of CRP were taken at pre-specified visits and were sent to the central laboratory for analysis. Change from Baseline in CRP was calculated as the Week 24 value minus the baseline value. CRP is an acute-phase protein whose plasma concentration increases in response to inflammation. CRP is a useful marker of inflammation.
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Timepoint [19]
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Baseline and Week 24
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Secondary outcome [20]
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Change From Baseline in ESR at Week 24
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Assessment method [20]
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ESR is measured by a blood test that shows the rate at which red blood cells sediment in a period of 1 hour. Blood samples for the determination of ESR were taken at pre-specified visits and were measured immediately at the trial site. Change from baseline in ESR was calculated as the Week 24 value minus the baseline value.
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Timepoint [20]
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Baseline and Week 24
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Secondary outcome [21]
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Change From Baseline in the Short-Form 36 (SF-36v2) Norm-based Scores for Physical Component Summary and Physical Items at Week 24
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Assessment method [21]
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The SF-36v2 is a standardized questionnaire used to measure overall subjective health status by measuring 8 health-related parameters (each scored from 0 [poorer health] to 100 [better health]): body pain, general mental health (MH), perception of general health, physical functioning, role limitations (RL) caused by mental condition, RL caused by a physical condition, social functioning, and vitality. It yields an 8-scale profile of functional health and well-being scores, as well as psychometrically based physical and MH summary measures and a preference-based health utility index.
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Timepoint [21]
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Baseline and Week 24
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Secondary outcome [22]
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Change From Baseline in the SF-36v2 Norm-based Scores for Mental Component Summary and Mental Items at Week 24
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Assessment method [22]
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The SF-36v2 is a standardized questionnaire used to measure overall subjective health status by measuring 8 health-related parameters (each scored from 0 [poorer health] to 100 [better health]): body pain, general mental health (MH), perception of general health, physical functioning, role limitations (RL) caused by mental condition, RL caused by a physical condition, social functioning, and vitality. It yields an 8-scale profile of functional health and well-being scores, as well as psychometrically based physical and MH summary measures and a preference-based health utility index.
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Timepoint [22]
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Baseline and Week 24
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Secondary outcome [23]
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Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Questionnaire Score at Week 24
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Assessment method [23]
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The FACIT-F score has a valid range of values from 0 to 52, with a higher score indicating a lower burden of fatigue. The subset determining fatigue contains 13 questions. Responses to each question were scored from 0, indicating "Not at all fatigued," to 4, indicating "Very much fatigued."
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Timepoint [23]
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Baseline and Week 24
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Secondary outcome [24]
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Change From Baseline in Levels of Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Week 24
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Assessment method [24]
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The following biomarkers were assessed: Anti-Cyclic Citrullinated Peptide 3 antibody (Anti-CCP), Rheumatoid factor IgA (RF-IgA), RF IgG (RF-IgG), and RF IgM (RF-IgM). Measurements of RF were used to characterize participants' disease activity and immune status. Anti-CCP was used to characterize the disease type and the immune status of the participants. Assessments for which results were below the lower limit of quantification (LLQ) were reported using a value of LLQ/2. Assessments for which results were above the upper limit of quantification (ULQ) were reported using a value of ULQ.
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Timepoint [24]
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Baseline and Week 24
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Secondary outcome [25]
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Change From Baseline in Levels of IL-6 and Serum Amyloid A at Week 24
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Assessment method [25]
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The following biomarkers were assessed: Interleukin 6 (IL-6) and Serum Amyloid A. These biomarkers were used to further characterize disease activity.
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Timepoint [25]
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Baseline and Week 24
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Secondary outcome [26]
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Minimum DAS28-ESR Score During the Double-blind (DB) and Open-label (OL) Periods, by Ofatumumab Treatment Course
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Assessment method [26]
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The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. The values summarized are the minimum DAS28 score (i.e. lowest level of disease activity) achieved by each participant within the first 24 weeks of each treatment course (TC), assessed using erythrocyte sedimentation rate (ESR; rate at which red blood cells sediment in 1 hour).
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Timepoint [26]
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First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [27]
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Minimum DAS28-CRP Score During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [27]
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The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. The values summarized are the minimum DAS28 score (i.e. lowest level of disease activity) achieved by each participant within the first 24 weeks of each treatment course, assessed using C-reactive Protein (CRP: used to monitor acute inflammatory phases of rheumatoid arthritis).
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Timepoint [27]
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First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [28]
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Minimum Change From Baseline in the DAS28-ESR Score, During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [28]
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The level of rheumatoid arthritis disease activity based on the DAS28 score is defined as low if DAS28 <=3.2, moderate if 3.2< DAS28 <=5.1, or high if DAS28 > 5.1. A DAS28 <2.6 corresponds to clinical remission. The values summarized are the minimum change from baseline DAS28 score (i.e. greatest change in disease activity during the treatment course) achieved by each participant within the first 24 weeks of each treatment course, assessed by using ESR. Baseline score was determined at the start of each treatment course. For change from baseline, participants had to have both a baseline DAS28 value for the treatment course (i.e., the latest value on or before the date of infusion A of the treatment course, providing it was done within a 14 day window prior to the date of infusion A) and a DAS28 value during the treatment course (i.e., during first 24 weeks of each treatment course). Change from baseline was calculated as the value during the treatment course minus the baseline value.
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Timepoint [28]
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0
First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [29]
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Minimum Change From Baseline in the DAS28-CRP Score, During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [29]
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The level of rheumatoid arthritis disease activity based on the DAS28 score is defined as low if DAS28 <=3.2, moderate if 3.2< DAS28 <=5.1, or high if DAS28 > 5.1. A DAS28 <2.6 corresponds to clinical remission. The values summarized are the minimum change from baseline DAS28 score (i.e. greatest change in disease activity during the treatment course) achieved by each participant within the first 24 weeks of each treatment course, assessed by using CRP. Baseline score was determined at the start of each treatment course. For change from baseline, participants had to have both a baseline DAS28 value for the treatment course (i.e., the latest value on or before the date of infusion A of the treatment course, providing it was done within a 14 day window prior to the date of infusion A) and a DAS28 value during the treatment course (i.e., during first 24 weeks of each treatment course). Change from baseline was calculated as the value during the treatment course minus the baseline value.
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Timepoint [29]
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First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [30]
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Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using ESR), During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [30]
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The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. Remission is defined as a DAS28 score <2.6 at any time during the first 24 weeks of each treatment course. Low disease activity is defined as a DAS28 score >=2.6 and <3.2 at any time during the first 24 weeks of each treatment course.
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Timepoint [30]
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First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [31]
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Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using CRP), During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [31]
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0
The DAS28 is a clinical index of rheumatoid arthritis disease activity that combines information from swollen and tender joints (jts.), the APR, and general health (patient global assessment). The following jts. were assessed on both sides of the body: shoulder, elbow, wrist, metacarpophalangeal (5 per side), proximal interphalangeal (5 per side), and knee. The level of disease activity can be interpreted as low (DAS28<=3.2), moderate (3.2<DAS28<=5.1), or high (DAS28>5.1); total score, 0-9.4. A DAS28 <2.6 corresponds to remission. Remission is defined as a DAS28 score <2.6 at any time during the first 24 weeks of each treatment course. Low disease activity is defined as a DAS28 score >=2.6 and <3.2 at any time during the first 24 weeks of each treatment course.
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Timepoint [31]
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First 24 weeks of each treatment course (assessed up to Week 144)
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Secondary outcome [32]
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Time to Retreatment, by Ofatumumab Treatment Course
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Assessment method [32]
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Time to retreatment is defined as the time in days between infusion A of each treatment course and infusion A of the following treatment course. For participants randomized to ofatumumab in the Double-blind Period, Treatment Course 1 refers to the course of ofatumumab received in the Double-blind Period. The minimum period allowed per protocol before retreatment was 24 weeks (end of Double-blind Period). For participants randomized to placebo in the Double-blind Period, Treatment Course 1 refers to the first course of ofatumumab received in the Open-label Period. The minimum period allowed per protocol before retreatment during the Open-label Period was 16 weeks.
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Timepoint [32]
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From Baseline up to Week 144
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Secondary outcome [33]
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Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event, During the DB and OL Periods, by Ofatumumab Treatment Course
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Assessment method [33]
0
0
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold >=2%) and SAEs.
Query!
Timepoint [33]
0
0
First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144
Query!
Secondary outcome [34]
0
0
Number of Participants With a CD19+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [34]
0
0
The number of participants with a CD19+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 giga [10^9] per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Query!
Timepoint [34]
0
0
From baseline up to Week 144
Query!
Secondary outcome [35]
0
0
Number of Participants With a CD3+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [35]
0
0
The number of participants with a CD3+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 giga [10^9] per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Query!
Timepoint [35]
0
0
From baseline up to Week 144
Query!
Secondary outcome [36]
0
0
Number of Participants With a CD4+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [36]
0
0
The number of participants with a CD4+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 giga [10^9] per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Query!
Timepoint [36]
0
0
From baseline up to Week 144
Query!
Secondary outcome [37]
0
0
Number of Participants With a CD8+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [37]
0
0
The number of participants with a CD8+ cell count greater than or equal to the lower limit of normal (LLN; reference range 0.11 to 0.66 giga [10^9] per liter) or the baseline value (whichever was lower) is presented. The baseline assessment is defined as the start of the Double-blind Period.
Query!
Timepoint [37]
0
0
From baseline up to Week 144
Query!
Secondary outcome [38]
0
0
Number of Participants With Vital Sign Data Outside the Clinical Concern Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [38]
0
0
The baseline value for a treatment course is defined as the value before infusion A of each treatment course. The post-baseline visit is defined as any assessment during or after the start of infusion A during the specified treatment course. Pre-defined limits of potential clinical concern for vital signs (Low, High) are: Diastolic blood pressure (DBP) (millimeters of mercury [mmHg]): 40, 110; Systolic blood pressure (SBP) (mmHg): 90, 170; Heart rate (beats per minute): 35, 120. LLN=lower limit of normal; ULN=upper limit of normal.
Query!
Timepoint [38]
0
0
From baseline up to Week 144
Query!
Secondary outcome [39]
0
0
Number of Participants With the Indicated Electrocardiogram (ECG) Findings, During the OL Period
Query!
Assessment method [39]
0
0
The number of participants with normal, abnormal clinically significant (CS), and abnormal not clinically significant (NCS) ECG findings, as well as the number of participants with no results (NR), during the OL Period are presented. An overall interpretation of the ECG was made by the investigator, or the investigator could delegate this task to a cardiologist, if applicable.
Query!
Timepoint [39]
0
0
From DB Period completion (Week 24) until the completion of the OL Period, assessed up to Week 144
Query!
Secondary outcome [40]
0
0
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [40]
0
0
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Baseline (BL) value for a treatment course (TC) is defined as the latest value on or before the date of infusion A of the TC. The post-baseline (PBL) visit is defined as any visit after the date of infusion A during the specified TC. Pre-defined limits of potential CC (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) are: Albumin: 0.9, 1.5; Alanine amino transferase (ALT): NA, 2; Alkaline phosphatase (ALP): NA, 1.5; Aspartate amino transferase (AST): NA, 2; Bilirubin total (TBIL): NA, 1.5; Calcium: 0.85, 1.08; CO2 content/bicarbonate (BCO): 0.85/0.75, 1.2/1.3, ; Chloride: 0.9, 1.1; Creatine kinase (CK): NA, 2; Creatinine: NA, 1.2; Gamma glutamyl transferase (GGT): NA, 2; Lactate dehydrogenase (LDH): NA, 2; Potassium: 0.9, 1.1; Sodium: 0.93, 1.07; Total protein: 0.8, 1.15; Urea/blood urea nitrogen (BUN): NA, 1.5; Uric acid: NA, 1.5.
Query!
Timepoint [40]
0
0
From baseline up to Week 144
Query!
Secondary outcome [41]
0
0
Number of Participants With the Indicated Hematology Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course
Query!
Assessment method [41]
0
0
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. The baseline (BL) value for a treatment course (TC) is defined as the latest value on or before the date of infusion A of the TC. The post-baseline (PBL) visit is defined as any visit after the date of infusion A during the specified TC. Pre-defined limits of potential clinical concern (CC Low [relative to lower limit of normal], CC High [relative to upper limit of normal]) are: Eosinophils: NA, 2; Hematocrit (HCT): 0.75, 1.2; Hemoglobin (Hb): 0.75, 1.2; Lymphocytes: 0.4, 2; Neutrophils total (TNUE): 0.8, 1.6; Platelet count (PC): 0.65, 1.5; Red blood cell count (RBC): 0.75, 2; White blood cell count (WBC): 0.7, 1.6.
Query!
Timepoint [41]
0
0
From baseline up to Week 144
Query!
Secondary outcome [42]
0
0
Number of Participants With the Indicated Biomarker Data Outside the Reference Range at Baseline or Any Post-Baseline Visit During the DB and OL Periods by Ofatumumab Treatment Course (TC)
Query!
Assessment method [42]
0
0
Only those parameters for a particular flag (<LLN or >ULN) are summarized if at least one value was outside the specified reference range. The Baseline (BL) value for a TC was defined as the latest value on or before the date of infusion A of the TC. However to be evaluable as a baseline value, assessments must have been conducted within a 14 day window prior to the date of infusion A. The post-baseline (PBL) was any visit after the date of infusion A during the specified TC. The pre-defined LLN for biomarkers are: B-lymphocyte stimulator (B-ls):<486.5 nanograms per Liter (ng/L); Interleukin-6 (IL-6):<0.31ng/L and Serum amyloid A: <1951 ng/mL. LLN was not defined for Rheumatoid factor (RF)-IgA, RF-IgG, RF-IgM or anti- cyclic citrullinated peptide (CCP) antibody and RF. The pre- defined ULN range for biomarkers (RF)-IgA: >6 units; RF-IgG:>6 units; RF-IgM:>6 units; Anti-CCP:>19.9999 units; B-ls:>1343.3 ng/L; IL-6: >5 ng/L; RF:>11.9999 kilounits (KU)/L; Serum amyloid A:>82432 ng/mL.
Query!
Timepoint [42]
0
0
From baseline up to Week 144
Query!
Secondary outcome [43]
0
0
Number of Participants With Any Serious Adverse Event During the Follow-up Period
Query!
Assessment method [43]
0
0
A serious adverse event is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general SAE module for a list of SAEs.
Query!
Timepoint [43]
0
0
From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from Last Subject Last Visit [LSLV])
Query!
Secondary outcome [44]
0
0
Number of Participants With Immunoglobulin Values Outside the Reference Range During the Follow-up Period
Query!
Assessment method [44]
0
0
The reference ranges for immunoglobulins (LLN, ULN) are defined as: IgA (grams/Liter): 0.81, 4.63; IgG (grams/Liter): 6.94, 16.18; IgM (grams/Liter): 0.48, 2.71.
Query!
Timepoint [44]
0
0
From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)
Query!
Secondary outcome [45]
0
0
Time to First CD19+ B-cell Repopulation Relative to the First Dose and Last Dose of Ofatumumab
Query!
Assessment method [45]
0
0
Time to first CD19+ B-cell repopulation (return to normal or baseline level) relative to the first dose was assessed only for those participants whose B-cells repopulated after receiving ofatumumab. Time to first CD19+ B-cell repopulation relative to the last dose of ofatumumab was assessed only for those participants whose B-cells repopulated during their last ofatumumab treatment course or follow-up.
Query!
Timepoint [45]
0
0
From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248)
Query!
Secondary outcome [46]
0
0
Number of Participants With a Positive JC Virus Test Result During the Follow-up Period
Query!
Assessment method [46]
0
0
Blood samples were collected for analysis of plasma/white blood cell JC Virus (JCV) using the polymerase chain reaction (PCR) assay. A positive JC Virus test result indicated the presence of JC Virus.
Query!
Timepoint [46]
0
0
From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)
Query!
Secondary outcome [47]
0
0
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern During the Follow-up Period
Query!
Assessment method [47]
0
0
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) are: ALT: NA, 2; ALP: NA, 1.5; Creatinine: N/A, 1.2; CO2/BCO: 0.85/0.75, 1.2/1.3; CK: NA, 2; GGT: NA, 2; Urea/BUN: NA, 1.5.
Query!
Timepoint [47]
0
0
From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)
Query!
Secondary outcome [48]
0
0
Number of Participants With the Indicated Hematology Values of Potential Clinical Concern During the Follow-up Period
Query!
Assessment method [48]
0
0
Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low [relative to lower limit of normal], CC High [relative to upper limit of normal]) are: Eosinophils: NA, 2; Total neutrophils: 0.8, 1.6; Platelet count: 0.65, 1.5.
Query!
Timepoint [48]
0
0
From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)
Query!
Eligibility
Key inclusion criteria
Inclusion Criteria
- Age = 18 years;
- Active disease at the time of screening as defined by:
= 8 swollen joints (of 66 joints assessed) and = 8 tender joints (of 68 joints
assessed), C-Reactive Protein (CRP) = 1.0 mg/dL or Erythrocyte Sedimentation Rate
(ESR) = 22 mm/hour, DAS28=3.2 (based on ESR);
- Inadequate response to previous or current methotrexate treatment;
- Treatment with methotrexate (MTX), 7.5-25 mg/week, for at least 12 weeks and at a
stable dose for at least 4 weeks.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
Exclusion Criteria
- Patients with a history of a rheumatic autoimmune disease other than RA or with
significant systemic involvement secondary to RA;
- Previous exposure to biologic anti-rheumatic therapies, including investigational
compounds;
- Previous exposure to biologic DMARDs; Chronic or ongoing active infectious disease
requiring systemic treatment;
- Clinically significant cardiac disease; History of significant cerebrovascular
disease;
- Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological,
cerebral psychiatric disease, or evidence of demyelinating disease;
- Known HIV positive; Serologic evidence of Hepatitis B infection; Positive test for
Hepatitis C; Positive plasma / white cell JC Virus PCR;
- Serum IgG < lower limit of normal;
- Breast feeding women or women with a positive pregnancy test at screening;
- Current participation in any other interventional clinical study;
- Patients known or suspected of not being able to comply with a study protocol.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/01/2008
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
15/07/2013
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
265
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Query!
Recruitment hospital [1]
0
0
GSK Investigational Site - Camperdown
Query!
Recruitment hospital [2]
0
0
GSK Investigational Site - Maroochydore
Query!
Recruitment hospital [3]
0
0
GSK Investigational Site - Clayton
Query!
Recruitment hospital [4]
0
0
GSK Investigational Site - Malvern
Query!
Recruitment hospital [5]
0
0
GSK Investigational Site - Shenton Park
Query!
Recruitment postcode(s) [1]
0
0
2050 - Camperdown
Query!
Recruitment postcode(s) [2]
0
0
4558 - Maroochydore
Query!
Recruitment postcode(s) [3]
0
0
3168 - Clayton
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Recruitment postcode(s) [4]
0
0
3144 - Malvern
Query!
Recruitment postcode(s) [5]
0
0
6008 - Shenton Park
Query!
Recruitment outside Australia
Country [1]
0
0
Argentina
Query!
State/province [1]
0
0
Buenos Aires
Query!
Country [2]
0
0
Argentina
Query!
State/province [2]
0
0
Santa Fe
Query!
Country [3]
0
0
Argentina
Query!
State/province [3]
0
0
Cordoba
Query!
Country [4]
0
0
Argentina
Query!
State/province [4]
0
0
Tucuman
Query!
Country [5]
0
0
Belgium
Query!
State/province [5]
0
0
Liège
Query!
Country [6]
0
0
Belgium
Query!
State/province [6]
0
0
Merksem
Query!
Country [7]
0
0
Chile
Query!
State/province [7]
0
0
Región Metro De Santiago
Query!
Country [8]
0
0
Chile
Query!
State/province [8]
0
0
Valparaíso
Query!
Country [9]
0
0
Czechia
Query!
State/province [9]
0
0
Ostrava Trebovice
Query!
Country [10]
0
0
Czechia
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State/province [10]
0
0
Praha 2
Query!
Country [11]
0
0
Czechia
Query!
State/province [11]
0
0
Zlin
Query!
Country [12]
0
0
Hungary
Query!
State/province [12]
0
0
Budapest
Query!
Country [13]
0
0
Hungary
Query!
State/province [13]
0
0
Gyor
Query!
Country [14]
0
0
Peru
Query!
State/province [14]
0
0
Callao
Query!
Country [15]
0
0
Peru
Query!
State/province [15]
0
0
Lima
Query!
Country [16]
0
0
Poland
Query!
State/province [16]
0
0
Bialystok
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Country [17]
0
0
Poland
Query!
State/province [17]
0
0
Bydgoszcz
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Country [18]
0
0
Poland
Query!
State/province [18]
0
0
Warszawa
Query!
Country [19]
0
0
Poland
Query!
State/province [19]
0
0
Wroclaw
Query!
Country [20]
0
0
Romania
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State/province [20]
0
0
Bucuresti
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Country [21]
0
0
Russian Federation
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State/province [21]
0
0
Ekaterinburg
Query!
Country [22]
0
0
Russian Federation
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State/province [22]
0
0
Moscow
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Country [23]
0
0
Russian Federation
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State/province [23]
0
0
Saint-Petersburg
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Country [24]
0
0
Russian Federation
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State/province [24]
0
0
Saratov
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Country [25]
0
0
Russian Federation
Query!
State/province [25]
0
0
Yaroslavl
Query!
Country [26]
0
0
South Africa
Query!
State/province [26]
0
0
Gauteng
Query!
Country [27]
0
0
South Africa
Query!
State/province [27]
0
0
Parow
Query!
Country [28]
0
0
Spain
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State/province [28]
0
0
Granada
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Country [29]
0
0
Spain
Query!
State/province [29]
0
0
Malaga
Query!
Country [30]
0
0
Spain
Query!
State/province [30]
0
0
Santander
Query!
Country [31]
0
0
Spain
Query!
State/province [31]
0
0
Sevilla
Query!
Country [32]
0
0
United Kingdom
Query!
State/province [32]
0
0
Lancashire
Query!
Country [33]
0
0
United Kingdom
Query!
State/province [33]
0
0
Cannock
Query!
Country [34]
0
0
United Kingdom
Query!
State/province [34]
0
0
Leytonstone, London
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Country [35]
0
0
United Kingdom
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State/province [35]
0
0
Maidstone
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
Query!
Country
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Ethics approval
Ethics application status
Query!
Summary
Brief summary
This is a phase III, double-blind, randomized, multicenter, and parallel group trial with a
duration of 24 weeks, followed by a 120 week Open-label Period. the primary purpose of the
study is to demonstrate the efficacy of ofatumumab in reducing clinical signs and symptoms in
adult RA patients after a single course of ofatumumab.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT00611455
Query!
Trial related presentations / publications
Taylor PC, Quattrocchi E, Mallett S, Kurrasch R, Petersen J, Chang DJ. Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial. Ann Rheum Dis. 2011 Dec;70(12):2119-25. doi: 10.1136/ard.2011.151522. Epub 2011 Aug 22.
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Public notes
Query!
Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
Query!
Address
0
0
GlaxoSmithKline
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Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00611455
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