E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
1. 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 2. To evaluate the impact on patient reported outcomes after repeated courses of ofatumumab 3. To evaluate the effect on established and novel biomarkers of clinical response after repeated courses of ofatumumab 4. To evaluate host immune response against ofatumumab after repeated courses of ofatumumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 or - 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 and 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 2); 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 at a later time 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.
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E.4 | Principal 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 the following treatments < 4 weeks prior to Visit 2A: Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies) 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 for: -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 a 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 within six 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 <LLN (as assessed by the central laboratory) at screening 18) Screening laboratory values: Hemoglobin <5.5 mmol/L (9.9 g/dL) Neutrophils <2 x 109/ L Platelets <100 x 109/ L CD4 (or CD4/CD8 ratio) < LLN 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 Hepatitis B (primary and secondary immunization and booster) will be considered negative 20) Positive plasma or white cell JC virus (JCV) PCR (either compartment) 21) Known hypersensitivity to components of the investigational medicinal product 22) Patients who have received treatment with any non-marketed drug substance <4 weeks prior to Visit 1 (screening) 23) Current participation in any other interventional clinical study except for study Hx-CD20-403 24) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 25) Breast feeding women or women with a positive pregnancy test at Visit 1 (screening) 26) Women of childbearing potential not willing to use adequate contraception during study and 1 year after last dose of ofatumumab. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, hormonal birth control injections and male partner sterilization if appropriate. For patients in the USA the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent). 27) RA functional class IV 28) Positive test for Hepatitis C Note i) Subjects who, in the same blood sample, are positive for HB C ab and have positive or indeterminable results of HB C RIBA immunoblot assay are excluded ii) Subjects who in the same blood sample are positive for HB C ab but negative for the HB C RIBA immunoblot assay may participate |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to treatment withdrawal, defined as the time from first infusion of ofatumumab until date of treatment withdrawal. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as date of the last patient attending the last visit, hence this will be when the last patient’s B-cells have returned to baseline or normal levels.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |