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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/NCT01753076
Registration number
NCT01753076
Ethics application status
Date submitted
17/12/2012
Date registered
20/12/2012
Date last updated
21/12/2017
Titles & IDs
Public title
Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
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Scientific title
Study NOG112264, a Phase II Study of Ozanezumab (GSK1223249) Versus Placebo in the Treatment of Amyotrophic Lateral Sclerosis
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Secondary ID [1]
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112264
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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:
Amyotrophic Lateral Sclerosis
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Condition category
Condition code
Neurological
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Neurodegenerative diseases
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Ozanezumab
Treatment: Drugs - Placebo
Experimental: Ozanezumab IV - Administered by IV route. Treatment period - 48 Weeks
Placebo Comparator: Placebo - Normal saline by IV route. Treatment period - 48 weeks
Treatment: Drugs: Ozanezumab
Ozanezumab injection solution
Treatment: Drugs: Placebo
Normal saline (0.9% sodium chloride) infusion
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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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Joint Rank Scores for Combined Analysis of Function (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised [ALSFRS-R] Score) and 48 Week Overall Survival
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Assessment method [1]
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The joint rank score is a combined assessment of function and survival. Function is assessed using change from Baseline in the ALSFRS-R total score. To calculate joint rank scores, every participant was compared with all other participants in a pair wise manner and assigned a score of -1, 0 or 1 based on their relative outcomes. A subject's joint rank score is the sum of their scores across the pair wise comparisons. The . The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing. Lower scores of ALSFRS-R reflect greater impairment.
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Timepoint [1]
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Week 48
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Secondary outcome [1]
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Change From Baseline in the ALSFRS-R Total Score at Week 48
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Assessment method [1]
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The rate of decline was estimated by the change from Baseline in ALSFRS-R. The monthly slope for the ALSFRS-R score (i.e., the monthly rate of decline) was calculated as change from Baseline in the ALSFRS-R score at the last visit for that treatment period divided by the study day at the last visit for that treatment period /30.4. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
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Timepoint [1]
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Baseline and Week 48
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Secondary outcome [2]
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Rate of Decline Over Week 48 in the ALSFRS-R Total Score
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Assessment method [2]
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The rate of decline was estimated by the change from Baseline in ALSFRS-R. The monthly slope for the ALSFRS-R score (i.e., the monthly rate of decline) was calculated as change from Baseline in the ALSFRS-R score at the last visit for that treatment period divided by the study day at the last visit for that treatment period devided by 30.4. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. The ALSFRS-R was a quickly administered (5 min) ordinal rating scale used to determine a participant's assessment of their capability and independence in 12 functional activities. There were 12 questions, graded by the participant 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.
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Timepoint [2]
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Baseline to Week 48
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Secondary outcome [3]
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Change From Baseline in Slow Vital Capacity (SVC) at Week 48
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Assessment method [3]
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SVC was measured by using a validated spirometer. Three SVC measurements were performed for each participant at each assessment provided the difference from the second trial (if arranged by the numerical value) was not greater than 10%. If the difference between the best and the next best (based on the largest numerical value) SVC value from the first three trials was greater than 10%, additional trials (up to 5 in total) could have been performed. The Week 0 (visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. A mixed-model repeated measures (MMRM) adjusted for treatment, visit, treatment by visit, Baseline SVC, Baseline SVC by visit, riluzole use. and country group was used for the analysis.
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Timepoint [3]
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Baseline and Week 48
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Secondary outcome [4]
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Change From Baseline in Muscle Strength as Measured by Hand Held Dynamometry (HHD) Score at Week 48
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Assessment method [4]
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The HHD is a device placed between the hand of the practitioner and the tested body part and provides a quantified measurement of muscle strength. Each muscle was tested twice, and both values were recorded. Additionally, a third trial could have been performed if the variability between the first two trials was greater than 15 % or if the rater thought that one of the first two trials was not valid. The Week 0 (Visit 2) value was considered to be the Baseline value. Percent change from Baseline for each muscle group was calculated as 100*(HHD score minus the Baseline score) divided by the Baseline score. The average percent change was the mean percent change across the muscle groups that were non-missing/non-zero at Baseline. MMRM adjusted for treatment, visit, treatment by visit, number of non-missing/non-zero muscle groups at Baseline, number of non-missing/non-zero muscle groups at Baseline by Visit, riluzole use, and country group was used for the analysis.
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Timepoint [4]
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Baseline and Week 48
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Secondary outcome [5]
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Number of Clinical Global Impression-improvement Scale (CGI-I) Responders at Week 48
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Assessment method [5]
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The CGI-I scale is a single observer-rated item measuring global improvement relative to Baseline. The CGI-I score is rated on a 7-point scale, from 1 (very much improved) to 7 (very much worse). Participant status at Baseline was assessed using the Clinical Global Impression Severity scale (CGI-S), which is a 7-point scale (1: normal, not at all ill; 7: most extremely ill) used to rate the severity of the participant's illness. Participants achieving a score of 1-4 in the CGI-I at Week 48 were considered to be responders. A a logistic regression adjusted for CGI-S at Baseline, riluzole use, and world region was used for the analysis.
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Timepoint [5]
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Week 48
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Secondary outcome [6]
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Overall Survival at Week 48 and Week 60
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Assessment method [6]
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Overall survival is defined as the time from randomization to death or censoring at the time point of analysis, whichever comes first. Kaplan Meier estimates at Week 48 were evaluated at Day 344. A participant was considered to have completed if he/she was censored at Day 344. Kaplan Meier estimates at Week 60 were evaluated at Day 428. A participant was considered to have completed if he/she was censored at Day 428. Confidence intervals were estimated using the Brookmeyer Crowley method. Results are shown as the estimated percentage of participants alive at Weeks 48 and 60. Week 48: Only on-treatment data (data within 21 days of the last dose) were analyzed. Week 60: Including off treatment data (data after 21 days after the last dose) were analyzed.
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Timepoint [6]
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Week 48 and Week 60
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Secondary outcome [7]
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Progression-free Survival at Week 48
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Assessment method [7]
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Progression-free survival at Week 48 is defined as the time from randomization to progression (decline of at least six points on the ALSFRS-R from Baseline) or death or censored at Week 48, whichever comes first. Kaplan Meier estimates at Week 48 were evaluated at Day 344. A participant was considered to have completed if he/she was censored at Day 344. Confidence intervals were estimated using the Brookmeyer Crowley method. Results are shown as the estimated percentage of participants alive and without disease progression at Week 48.
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Timepoint [7]
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Week 48
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Secondary outcome [8]
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Change From Baseline in the EuroQol 5 Dimensions-5 Level Short Form (EQ-5D-5L) Utility Score at Week 48
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Assessment method [8]
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A utility score for each participant was calculated based on the value set for England. The Week 0 (Visit 2) value was considered to be the Baseline value. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. EQ-5D-5L is a standardized, participant-rated instrument for use as a measure of health outcomes. The EQ 5D-5L includes 2 components: the EQ-5D-5L descriptive system and the EQ-Visual Analog Scale (EQ-VAS). The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). . For each of these dimensions, the participant self assigned a score: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems); 5 (extreme problems).Minimum score on scale was 1 and maximum score was 5 for each dimension. A negative change from Baseline indicates improvement.
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Timepoint [8]
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Baseline and Week 48
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Secondary outcome [9]
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Change From Baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) Total Score at Week 48
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Assessment method [9]
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The ALSAQ-40 is a disease specific health status assessment for individuals with ALS/motor neuron disease. The ALSAQ-40 is comprised of 40 questions measuring 5discrete dimensions of health status that are affected by the disease: physical mobility (10 items); activities of daily living and independence (10 items); eating and drinking (3 items); communication (7 items); emotional reactions (10 items). Participants were asked to indicate the frequency of each event by selecting one of five options (Likert scale: 0-4): never/rarely/sometimes/often/ always or cannot do at all. The total score (minimum possible score=0, maximum possible score=160) was calculated by adding the five domain scores. A low score indicates a better health state. Change from Baseline was calculated by subtracting the derived Baseline value from the post-Baseline value. A mixed-model repeated measures adjusted for treatment, Visit, Treatment by Visit, and Baseline ALSAQ-40 total score was used for the analysis.
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Timepoint [9]
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Baseline and Week 48
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Eligibility
Key inclusion criteria
- Patients with diagnosis of familial or sporadic ALS
- Onset of muscle weakness no more than 30 months before screening visit.
- Slow Vital Capacity (SVC) of at least 65% predicted for gender, age, ethnicity and
height at Screening.
- If on riluzole, the dose must have been stable for at least 28 days prior to Baseline
visit.
- Age 18 - 80 years inclusive.
- Female subjects may participate if they are of non-child-bearing potential or if they
are of child-bearing potential they must agree to use the approved contraceptive
methods
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2x upper limit
of normal (ULN); alkaline phosphatase and bilirubin <=1.5xULN.
- QTc (both QTcB and QTcF) <450 milliseconds (msec) or <480 msec for subjects with
Bundle Branch Block at Screening and Baseline (average from triplicate ECGs).
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Minimum age
18
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Maximum age
80
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Patients with other neuromuscular disorders (including a history of polio) which in
the opinion of the investigator could have contributed to the muscular atrophy or
weakness caused by ALS
- Patients with primary lateral sclerosis, monomelic ALS, ALS Parkinsonism dementia
complex.
- Patients requiring non-invasive or mechanical ventilation (non-invasive ventilation
for sleep apnoea is allowed subject to discussion with Medical Monitor)
- Patients on diaphragmatic pacing.
- Presence of any of the following clinical conditions: Drug abuse or alcoholism,
uncontrolled hypertension, active major infectious disease, unstable psychiatric
illness within 90 days of the Screening visit
- Subjects, who in the investigator's judgement, pose a significant suicide risk. -
Current or chronic history of liver disease, known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones), positive
Hepatitis B surface antigen or Hepatitis C antibody test.
- Subjects who have participated in a clinical trial involving receipt of a
biopharmaceutical product within 6 months prior to the first dosing day.
- Exposure to non-biological experimental agents 1 month or 5 half-lives prior to
Baseline visit (whichever is longer).
- History of sensitivity to ozanezumab, or components thereof, or a history of other
allergies that, in the opinion of the investigator, contraindicates participation in
the study.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
20/12/2012
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
22/01/2015
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Sample size
Target
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Accrual to date
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Final
304
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Recruitment in Australia
Recruitment state(s)
NSW,QLD
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Recruitment hospital [1]
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GSK Investigational Site - Randwick
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Recruitment hospital [2]
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GSK Investigational Site - Herston
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Recruitment postcode(s) [1]
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2031 - Randwick
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Recruitment postcode(s) [2]
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4029 - Herston
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Recruitment outside Australia
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United States of America
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State/province [1]
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Massachusetts
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United States of America
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Michigan
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United States of America
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New York
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United States of America
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Ohio
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Belgium
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Leuven
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Quebec
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France
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Lille cedex
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France
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Limoges cedex
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France
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Montpellier cedex 5
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France
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Nice cedex 3
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France
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Paris cedex 13
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Germany
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Baden-Wuerttemberg
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Germany
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Bayern
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Thueringen
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Germany
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Berlin
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Italy
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Piemonte
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Italy
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Veneto
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Japan
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Kanagawa
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Japan
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Miyagi
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Japan
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Osaka
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Korea, Republic of
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Seoul
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Netherlands
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Utrecht
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United Kingdom
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Lancashire
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United Kingdom
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Brighton
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United Kingdom
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Edgbaston,
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a 48-week, randomised, multi-centre, double-blind, placebo-controlled, parallel group
investigation of the efficacy and safety of intravenous (IV) ozanezumab (GSK1223249) compared
to placebo in subjects with Amyotrophic Lateral Sclerosis (ALS). Following a screening period
of up to four weeks, eligible subjects will be randomised (1:1) to receive IV placebo or 15
milligram (mg)/ kilogram (kg) IV ozanezumab every 2 weeks for a period of 48 weeks with a
follow-up visit around 14 weeks after the last infusion. A total of approximately 294
eligible subjects will be randomised from approximately 37 centers worldwide. The primary
objective is to assess the effect of ozanezumab on the physical function and survival of ALS
subjects over a treatment period of 48 weeks. Function will be measured using the ALS
Functional Rating Scale - Revised (ALSFRS-R). Secondary objectives include the evaluation of
other clinical outcomes associated with ALS (respiratory function, muscle strength,
progression free survival and overall survival) in support of the primary objective. Quality
of life, safety, tolerability, immunogenicity and pharmacokinetics (ozanezumab and riluzole)
will also be assessed.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01753076
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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GSK Clinical Trials
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Address
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GlaxoSmithKline
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01753076
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