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 TNF-alfa; antagonist therapy - ND
- Conditions
- Rheumatoid arthritisMedDRA version: 9.1Level: HLTClassification code 10039078Term: Rheumatoid arthropathies
- Registration Number
- EUCTR2007-002951-18-IT
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
1) Age > or equal 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: > or equal 8 swollen joints (of 66 joints assessed) and > or equal 8 tender joints (of 68 joints assessed) and C-Reactive Protein (CRP) > or equal 1.0 mg/dL or Erythrocyte Sedimentation Rate (ESR) > or equal 22 mm/hour (using Becton Dickinson Seditainer) and DAS28 > or equal 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 < o equal 3 days prior to Visit 2. 4) RA functional class I, II or III 5) Inadequate response to previous or current > or equal antagonist treatment after infliximab therapy (> or equal mg/kg; at least 4 infusions), or adalimumab therapy (40 mg every other week for > or equal 3 months), or etanercept therapy (25 mg twice weekly or 50 mg once a week for > or equal 3 months) defined as: Inadequate efficacy according to the investigator?s judgment and/or Intolerance defined as one or more side effects following at least one administration of one of the TNF alfa antagonists at the dose listed above that reasonably results in the discontinuation of treatment with the TNFalfa antagonist treatment 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 7.5 mg per week are permitted for patients who can 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
1) Patients with a history of a rheumatic autoimmune disease other than RA (except secondary Sjögren's syndrome, significant systemic involvement secondary to RA 2) Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds 3) Exposure to etanercept < or equal 4 weeks, infliximab or adalimumab < or equal 8 weeks, or abatacept < or equal 12 weeks prior to Visit 2 4) Received any of the following treatments within 4 weeks prior to Visit 2: - Anti-cancer therapy - Glucocorticoid < or equal 10 mg of prednisolone /day - Intra-articular, i.m. or i.v. corticosteorids - Live/attenuated vaccinations - Hydroxychloroquine - Cyclosporine - Azathioprine - Penicillamine 5) Exposure to sulfasalazine within 6 weeks prior to Visit 2 6) Exposure to leflunomide within 12 weeks prior to Visit 2 unless the patient has completed peroral cholestyramine treatment for washout according to locally accepted clinical practices 7) Exposure to gold therapy < or equal 12 weeks prior to Visit 2 8) Exposure to i.v. immunogammaglobulins < or equal 24 weeks prior to Visit 2 9) Past or current malignant melanoma 10) Past or current malignancy, except for: - Cervical carcinoma Stage 1B or less - Non-invasive basal cell and squamous cell skin carcinoma - Other cancer with complete response duration of > 5 years 11) 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 12) 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 13) 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 14) History of significant cerebrovascular disease 15) Known HIV positive 16) 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) 17) Positive serology for hepatitis B (HB) defined as: - Positive test for HBsAg and/or - Positive test for anti-HBc and anti-HBs Patients with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will be considered negative 18) Positive plasma / white cell JC Virus (JCV) PCR (either compartment) 19) Known hypersensitivity to components of the investigational medicinal product 20) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to screening 21) Current participation in any other interventional clinical study 22) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 23) Breast feeding women or women with a positive pregnancy test at screening 24) Women of childbearing potential not willing to use adequate contraception during study and one year
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate efficacy of ofatumumab in reducing clinical signs and symptoms in adult RA patients after a single course of ofatumumab;Secondary Objective: 1) To evaluate long-term efficacy of repeated courses of ofatumumab 2) To evaluate the effect on established and novel biomarkers of clinical response after single and repeated courses of ofatumumab 3) To evaluate ofatumumab with respect to impact on patient reported outcomes after single and repeated courses of ofatumumab 4) To evaluate the risk of host immune response against ofatumumab after single and repeated courses of ofatumumab 5) To evaluate the safety of ofatumumab after single and repeated courses of ofatumumab;Primary end point(s): ACR20 at 24 weeks
- Secondary Outcome Measures
Name Time Method