A double-blind, randomized, placebo controlled, parallel group, multi-center, phase III trial of ofatumumab investigating clinical efficacy and safety in adult patients with active rheumatoid arthritis receiving non-biologic background disease-modifying antirheumatic drugs - ND

Conditions: Rheumatoid arthritis
MedDRA version: 9.1Level: HLTClassification code 10039078Term: Rheumatoid arthropathies

Registration Number: EUCTR2007-002945-18-IT

Lead Sponsor: GENMAB A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1000

Inclusion Criteria

1) Age > o 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: - > o equal 6 swollen joints (of 66 joints assessed) and - > o equal 6 tender joints (of 68 joints assessed) and 20 mm on the patient?s global VAS disease score and DAS28 < o equal 3.2 (based on ESR) Note: The swollen and tender joint counts will be re-assessed 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 feasible it can be done < o equal 3 days prior to visit 2. 4) RA functional class I, II or III 5) Treatment with 1 non-biologic DMARD for at least 12 weeks and at a stable dose for at least 4 weeks prior to Visit 2 (please refer to table 9 for permitted DMARDs) 6) 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, significant systemic involvement secondary to RA (vasculitis, pulmonary fibrosis or Felty's syndrome) 2) Previous exposure to biologic cell depleting anti-rheumatic therapies, including investigational compounds Exposure to etanercept < o equal 4 weeks, infliximab or adalimumab < o equal 8 weeks, or abatacept < o equal 12 weeks prior to Visit 2 4) Received any of the following treatments within 4 weeks prior to Visits 2: - Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies) - Glucocorticoid unless given in doses equivalent to < o equal 10 mg of prednisolone /day - Intra-articular, i.m. or i.v. corticosteorids - Live/attenuated vaccinations - Cyclosporine - Azathioprine - Penicillamine 5) Exposure to gold therapy < o equal 12 weeks prior to Visit 2 6) Exposure to i.v. immunogammaglobulins < o equal 24 weeks prior to Visit 2 7) Past or current malignant melanoma 8) 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 9) 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 10) 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 11) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, or evidence of demyelinating disease 12) History of significant cerebrovascular disease 13) Known HIV positive 14) Screening laboratory values (according to central laboratory): - Hemoglobin < 5.6 mmol/L (9.0 g/dL) - Neutrophils < 2 x 10 9/ L - Platelets < 100 x 10 9/ 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) 15) 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 will be considered negative. 16) Positive plasma or white cell JC virus PCR (either compartment) 17) Known hypersensitivity to components of the investigational medicinal product 18) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to screening 19) Current participation in any other interventional clinical study 20) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 21) Breast feeding women or women with a positive pregnancy test at screening 22) Women of childbearing potential not willing to use adequate contraception during study and one year after last dose of ofatumumab. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal

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;Secondary Objective: 1) To evaluate the safety after single and repeated courses of ofatumumab 2) To evaluate long-term efficacy of repeated courses of ofatumumab 3) To evaluate the effect on established and novel biomarkers of clinical response after single and repeated courses of ofatumumab 4) To evaluate the impact on patient reported outcomes after single and repeated courses of ofatumumab 5) To evaluate the risk of host immune response against ofatumumab after single and repeated courses of ofatumumab;Primary end point(s): ACR20 at 24 weeks

Secondary Outcome Measures