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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/NCT00686868




Registration number
NCT00686868
Ethics application status
Date submitted
28/05/2008
Date registered
30/05/2008
Date last updated
26/06/2017

Titles & IDs
Public title
Study to Evaluate SC Route of Administration of Ofatumumab in RA Patients
Scientific title
Clinical Phase I/IIA Study of Subcutaneously Administration of Ofatumumab in Rheumatoid Arthritis Patients on Stable Dose Methotrexate
Secondary ID [1] 0 0
OFA110867
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - placebo
Treatment: Drugs - ofatumumab

Experimental: 30mg - active

Experimental: 3mg - active

Experimental: 0.3mg - active

Placebo Comparator: placebo - placebo

Experimental: 60mg - 60mg

Experimental: 100mg - 100mg


Other interventions: placebo
placebo

Treatment: Drugs: ofatumumab
fully human anti-CD20 monoclonal antibody
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety and tolerability as described by the incidence and severity of adverse events [AEs], clinical laboratory parameters and vital signs.
Timepoint [1] 0 0
throughout the study
Secondary outcome [1] 0 0
Requirement for the use of pre-medication, including the timing, type and dose required.
Timepoint [1] 0 0
throughout study
Secondary outcome [2] 0 0
Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine fluorescent activated cell sorting (FACS) analysis.
Timepoint [2] 0 0
throughout study
Secondary outcome [3] 0 0
PK/PD parameters including estimation of time to re-population of CD-19 peripheral blood B-cells to above LLQ (and/or <95% depletion) following single subcutaneous dose of Ofatumumab.
Timepoint [3] 0 0
throughout study
Secondary outcome [4] 0 0
Immunogenicity as measured by the incidence, titre and type of human anti-human antibody (HAHA) immune response.
Timepoint [4] 0 0
throughout study
Secondary outcome [5] 0 0
Other pharmacodynamic/biomarkers of disease activity and immune status may include high sensitivity C-reactive protein (hsCRP), Erythrocyte Sedimentation Rate (ESR), B-Lymphocyte Stimulator (BLyS/BAFF), B-Lymphocyte Chemokine (BLC), IL-6,
Timepoint [5] 0 0
throughout study
Secondary outcome [6] 0 0
Immunoglobulins (IgA, IgG, IgM), Complement (CH50, C3, C4), IgM Rheumatoid Factor (IgM-RF), IgA-RF and IgG-RF, anti-cyclic citrullinated peptide antibody (aCCP),
Timepoint [6] 0 0
throughout study
Secondary outcome [7] 0 0
serum amyloid A (SAA), CD-3+, CD-4+ and CD-8+ lymphocytes or other biomarkers, as data permit.
Timepoint [7] 0 0
throughout study
Secondary outcome [8] 0 0
Pharmacodynamics (B-cell depletion and re-population) as measured by CD-19 peripheral blood B- lymphocyte count via routine FACS analysis.Other Secondary Endpoints
Timepoint [8] 0 0
throughout study

Eligibility
Key inclusion criteria
Key

- Male or female aged = 18 years

- A diagnosis of rheumatoid arthritis according to the American College of Rheumatology
(ACR1987 classification) of at least six months prior to screening

- Subjects must be treated with MTX, 7.5-25 mg/week, for at least 12 weeks prior to
Visit 2, with the last 4 weeks prior to Day 2 at a stable dosage

- Patient must be willing to receive folic acid =5mg/wk 4 weeks prior to baseline
administered according to locally accepted practice

- Body mass index (BMI) < 35kg/m2 (inclusive)

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with a history of a rheumatic autoimmune disease other than RA (except
secondary Sjögren's syndrome), or with significant systemic involvement secondary to
RA (vasculitis, pulmonary fibrosis or Felty's syndrome)

- Previous exposure to biologic cell depleting anti-rheumatic therapies, including
investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22,
anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, anti-CD52)

- Exposure to etanercept < 4 weeks, infliximab or adalimumab < 8 weeks, or abatacept or
anakinra < 12 weeks prior to visit 2

- Received any of the following treatments within 4 weeks prior to Visit 2:

- Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues,
monoclonal antibodies)

- Glucocorticoid unless given in doses equivalent to = 10 mg of prednisolone /day

- Intra-articular, i.m. or IV corticosteroids

- Live/attenuated vaccinations

- Cyclosporine

- Azathioprine

- Penicillamine

- Sulfasalazine

- Bucillamine

- Hydroxychloroquine

- Chloroquine

- Exposure to leflunomide within 12 weeks prior to visit 2 unless the subject has
completed peroral cholestyramine treatment

- Exposure to gold therapy = 12 weeks prior to Visit 2

- Exposure to IV immunogammaglobulins = 24 weeks prior to Visit 2

- Past or current malignant melanoma

- Chronic or ongoing active infectious disease requiring systemic treatment such as, but
not limited to, renal infection, chest infection with bronchiectasis, tuberculosis and
active hepatitis B and C

- History of significant cerebrovascular disease

- Positive plasma / white cell JC Virus (JCV) PCR (either compartment)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/06/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/05/2011
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [2] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [3] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [4] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
Belgium
State/province [3] 0 0
Brussels
Country [4] 0 0
Belgium
State/province [4] 0 0
Leuven
Country [5] 0 0
France
State/province [5] 0 0
Echirolles
Country [6] 0 0
Italy
State/province [6] 0 0
Veneto
Country [7] 0 0
New Zealand
State/province [7] 0 0
Christchurch
Country [8] 0 0
Poland
State/province [8] 0 0
Bydgoszcz
Country [9] 0 0
Russian Federation
State/province [9] 0 0
Moscow
Country [10] 0 0
Russian Federation
State/province [10] 0 0
Ryazan
Country [11] 0 0
Russian Federation
State/province [11] 0 0
Smolensk
Country [12] 0 0
Russian Federation
State/province [12] 0 0
Yaroslavl
Country [13] 0 0
Spain
State/province [13] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will examine the safety and tolerability, PK and PD of subcutaneously administered
GSK1841157 in patients with RA on stable dose Methotrexate. The study comprises a single dose
escalation/de-escalation phase to investigate the minimal efficacious dose based on PD
markers with an acceptable safety profile.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00686868
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00686868