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 had an inadequate response to methotrexate therapy - Investigating clinical efficacy of ofatumumab in RA patients who had an inadequate response to MTX

Conditions: Rheumatoid Arthritis
MedDRA version: 13.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Registration Number: EUCTR2007-002950-42-PL

Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 248

Inclusion Criteria

1) Age = 18 years
2) A diagnosis of rheumatoid arthritis according to the American College of Rheumatology (ACR1987 classification) of at least six months’ duration from diagnosis at screening
3) 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)
and
- C-Reactive Protein (CRP) = 1.0 mg/dL or Erythrocyte Sedimentation Rate (ESR) = 22 mm/hour
and
- DAS28=3.2 (based on ESR)
Note: The swollen and tender joints must be reassessed at baseline (Visit 2) to ensure these eligibility criteria are fulfilled prior to randomization. Where possible joint count reassessment must be performed at the baseline visit (Visit 2); if this is not possible it can be performed = 3 days prior to Visit 2.
4) RA functional class I, II or III
5) Inadequate response to previous or current methotrexate treatment defined as:
i) Inadequate efficacy according to the investigator’s judgment following at least 12 weeks of treatment receiving at least 15 mg methotrexate per week
and/or
ii) Intolerance defined as one or more side effects during treatment with at least 15 mg per week for at least two weeks, that reasonably results in the discontinuation or reduction in dose of methotrexate
6) Treatment with methotrexate (MTX), 7.5-25 mg/week, for at least 12 weeks and at a stable dose for at least 4 weeks prior to Visit 2. Doses of MTX as low as 7.5mg per week are permitted for patients who could not tolerate higher doses
7) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity including wash-out of other drug products is carried out
France: In France, a patient will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Patients 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)
2) Previous exposure to biologic anti-rheumatic therapies (with exceptions specified in (3)), including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, CAMPATH, anti-IL6 receptor)
3) Previous exposure to biologic DMARDs
4) 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 i.v. corticosteorids
- Live/attenuated vaccinations
- Cyclosporine
- Azathioprine
- Penicillamine
- Bucillamine
- Chloroquine
- Hydroxychloroquine
- Sulfasalazine
5) Exposure to leflunomide within 12 weeks prior to Visit 2 unless the patient has completed peroral cholestyramine treatment for washout according to manufacturer's instructions and locally accepted clinical practices
6) Exposure to gold therapy = 12 weeks prior to Visit 2
7) Exposure to i.v. immunogammaglobulins = 24 weeks prior to Visit 2
8) Past or current malignant melanoma
9) Past or current malignancy, except for:
- Cervical carcinoma Stage 1B or less
- Non-invasive basal cell and squamous cell skin carcinoma
- Other cancer with a complete response duration of > 5 years
10) Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis B and C
Note 1) Subjects with screening chest X-ray suggestive of TB without adequate TB treatment documented should be excluded 2) Subjects with positive skin tuberculin test should be excluded if judged at risk of latent TB infection.
11) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from screening, congestive heart failure, known QT abnormalities, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
12) 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
13) History of significant cerebrovascular disease
14) Known HIV positive
15) Screening laboratory values (according to central laboratory):
- Hemoglobin < 5.6 mmol/L (9.0 g/dL)
- Neutrophils < 2 x 109/ L
- Platelets < 100 x 109/ L
- Serum IgG < lower limit of normal
- S-ALAT > 3.0 times the upper limit of normal
- S-AST > 1.5 times the upper limit of normal
- S-ALP > 2 times the upper limit of normal
- S-creatinine > 133 µmol/L (1.5 mg/dL)
16) Positive serology for hepatitis B (HB) defined in terms of HBsAg, anti-HBc and anti-HBs antibodies:
- Patients positive for HBsAg should be excluded
- Patients negative for HBsAg and anti-HBs antibody, but positive for anti-HBc antibody should be tested for HB DNA and if positive excluded.
Patients with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will be considered negative
17) Positive for Hep C antibody and positive or indeterminant Hep C RIBA immunoblot.
1

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the efficacy of ofatumumab in reducing clinical signs and symptoms in adult RA patients after a single course of ofatumumab;Primary end point(s): ACR20 at 24 weeks;Secondary Objective: 1) To evaluate long-term efficacy of repeated courses of ofatumumab<br>2) To evaluate the effect on biomarkers of clinical response after single and repeated courses of ofatumumab<br>3) To evaluate ofatumumab with respect to impact on patient reported outcomes after single and repeated courses of ofatumumab<br>4) To evaluate the risk of host immune response against ofatumumab after single and repeated courses of ofatumumab<br>5) To evaluate the safety of ofatumumab after single and repeated courses of ofatumumab<br>

Secondary Outcome Measures