An open-label, international, multi-center, phase II, extension trial investigating long-term efficacy and safety of repeated treatment courses of ofatumumab, a fully human monoclonal anti-CD20 antibody, in adult patients with active rheumatoid arthritis who previously received ofatumumab or placebo in Trial Hx-CD20-403 - Long-term efficacy and safety of repeated ofatumumab courses in RA patients who were in Hx-CD20-403

• Conditions: Rheumatoid Arthritis; MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

• Registration Number: EUCTR2007-004878-31-DK
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-09
• Last Update Posted: 2 June 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 264

Inclusion Criteria

1) Previously received ofatumumab or placebo in Trial Hx-CD20-403
2) Applicable only to patients on methotrexate therapy at time of screening:
•Treatment with a stable dose of methotrexate (7.5 – 25 mg/week, p.o., i.m., and/or s.c.) = 4 weeks prior to visit 2A and
•Treatment with methotrexate = 12 weeks prior to Visit 2A, with possible interruption of treatment of maximum two weeks in total, in the period 5-12 weeks from baseline.
3) Applicable only to patients on oral corticosteroids therapy at time of screening:
•Treatment with a stable dose of oral corticosteroids (= 10 mg/day prednisolone or equivalent) = 4 weeks prior to visit 2A
4) Active disease at the time of screening as defined as:
•= 3 swollen joints (of 28 joints assessed) and
•= 3 tender joints (of 28 joints assessed) and
•DAS28=3.2 (based on ESR)
Note:
a) To accommodate for fluctuations in joint swelling, tenderness and ESR these assessments may be repeated once during the 14 day period from the screening visit to the baseline visit (Visit 2A), to meet requirements for inclusion criterion 4.
b) The swollen and tender joints should be reassessed at baseline (Visit 2A). Where possible, joint count reassessment should be performed at the baseline visit (Visit 2A); if this is not possible it can be performed = 3 days prior to Visit 2A. If the patient does not have = 3 swollen and tender joints at Visit 2A, this visit may be repeated once within the following 4 week period.
c) If joint counts at the repeated Visit 2A (if applicable) are still not meeting eligibility criterion no. 4, then Visit 1 and Visit 2A may be repeated several times within the recruitment period.
5) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out.

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) Use of DMARDs other than MTX < 4 weeks prior to Visit 2A. Use of leflunomide < 12 weeks prior to Visit 2A, unless peroral cholestyramine washout treatment completed according to local practice.
2) Exposure to other cell depleting therapy, including investigational compounds (e.g. anti-CD11a, anti-CD19, anti-CD20, anti-CD22, anti-BLyS/BAFF, anti-CD3, anti-CD4, anti-CD5, CAMPATH) < 6 months prior to Visit 2A.
3) Exposure to etanercept or anakinra < 4 weeks, infliximab or adalimumab < 8 weeks, or abatacept < 12 weeks prior to Visit 2A
4) Received any of following treatments < 4 weeks prior to Visit 2A:
•Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies)
•Oral corticosteroids > 10 mg prednisolone per day or equivalent
•Intra-articular, i.m. or i.v. corticosteorids
•Live/attenuated vaccinations
•Cyclosporine
•Azathioprine
•Penicillamine
•Mycophenolate Mufetil
5) Exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents < 5 years prior to screening
6) Exposure to gold therapy <12 weeks prior to Visit 2A
7) Exposure to i.v. immunogammaglobulins < 24 weeks prior to Visit 2A
8) Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy
9) Diagnosis of fibromyalgia or other chronic pain syndrome requiring daily narcotic treatment
10) History of infected joint prosthesis <5 years before Visit 1 and infected native joints <1 year before Visit 1
11) Past or current malignancy, except:
•Cervical carcinoma Stage 1B or less
•Non-invasive basal cell and squamous cell skin carcinoma
•Malignant melanoma with complete response of duration of > 10 years
•Other cancer diagnoses with complete response of duration of > 5 years
12) Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, TB and active hepatitis B and C.
Note i) Subjects with screening chest X-ray suggestive of TB without documented adequate TB treatment will be excluded; ii) Screening for latent TB infection using intradermal injection of tuberculin should be conducted according to local guidelines. Subjects with a positive skin tuberculin test should be excluded if investigator judges patient at risk of latent TB infection.
13) Clinically significant cardiac disease including unstable angina, acute myocardial infarction < 6 months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
14) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
15) History of significant cerebrovascular disease
16) Known or suspected HIV positive
17) A circulating IgG level 18) Screening laboratory values:
Hemoglobin < 6.2 mmol/L (9.9 g/dL)
Neutrophils < 2 x 109/ L
Platelets < 100 x 109/ L
CD4 (or CD4/CD8 ratio)S-ALAT > 3 times ULN
S-ALP > two times ULN
S-AST > 1.5 x ULN
S-creatinine > 133 µmol/L (1.5 mg/dL)
19)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 HB (primary and secondary immunization and booster) will be conside

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the long-term effectiveness of repeated courses of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403;Secondary Objective: •To evaluate the long-term safety of repeated courses of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403<br>•To evaluate the impact on patient reported outcomes after repeated courses of ofatumumab <br>•To evaluate the effect on established and novel biomarkers of clinical response after repeated courses of ofatumumab<br>•To evaluate host immune response against ofatumumab after repeated courses of ofatumumab.<br>;Primary end point(s): Time to treatment withdrawal, defined as the time from first infusion of ofatumumab until date of treatment withdrawal.