E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Rheumatoid arthritis (RA) |
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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 | PT |
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 efficacy of 5 dose regimens of BG9924 when administered in combination with MTX to subjects with active RA who have had an inadequate response to conventional DMARD therapy. The primary efficacy outcome measure is the proportion of subjects with ACR50 at Week 14. To achieve ACR50 response, a 50% improvement compared to baseline is required for both swollen and tender joint counts, as well as 3 out of 5 additional parameters: subject’s global assessment of disease activity, Investigator’s global assessment of disease activity, subject’s assessment of pain, HAQ-DI, and hsCRP or ESR. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of this study are as follows: - To assess the safety and tolerability of these 5 dose regimens of BG9924 in this patient population. - To assess the PK and PD profile of these 5 dose regimens of BG9924 in this patient population.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Study sites may choose to participate in an optional PK sub-study. Approximately 50 consenting subjects will have 6 additional visits following Visits 1 (Visits 1a and 1b), 3 (Visit 3a), and 8 (Visits 8a, 8b, and 8c). Blood samples for FACS analysis will also be taken from subjects participating in this sub-study. Objectives: -To assess the PK and PD profile of these 5 dose regimens of BG9924 in this patient population. |
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E.3 | Principal inclusion criteria |
Candidates must meet the following eligibility criteria at Day 0 (Visit 1/Week 0): 1. Must give written informed consent and any authorizations required by local law (e.g., Protected Health Information [PHI]). 2. Aged 18 to 75 years old, inclusive, at the time of informed consent. 3. Must have a diagnosis of adult onset RA according to the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis (Functional Class I–III) (Appendix A) for at least 6 months prior to Day 0. 4. Must have been treated with, and be tolerating, MTX (> or=10 mg/week to < or =25 mg/week) for at least 3 months immediately prior to Day 0. The dose of MTX must be stable for at least 4 weeks prior to D0. 5. Must have had an inadequate response to at least 1 conventional DMARD therapy (i.e., MTX, leflunomide, sulfasalazine, etc.) due to inadequate efficacy or toxicity. 6. Must have a Swollen Joint Count (SJC) > or =8 and a Tender Joint Count (TJC)> or =8 (66/68 joint count at Screening). 7. Must have elevated hsCRP > or =1.5 times the upper limit of normal (ULN) or ESR > or = 28 mm/hr at Screening. 8. Must be willing to receive oral folate (> or =5 mg/week) for the duration of the study.
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E.4 | Principal exclusion criteria |
MEDICAL HISTORY 1. Subjects with body weight <50kg 2. Subjects with history of malignancy or carcinoma in situ (subjects with history of excised or treated basal cell carcinoma are eligible to participate in this study) 3.Subjects with a mole or lesion currently undiagnosed, but suspicious for malignancy. Any suspicious skin lesion should be evaluated and excised by a dermatologist prior to inclusion in the study 4.History of clinically significant (as determined by Investigator) cardiac, allergic, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal or hematologic insufficiency, or any major disease that could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinsons disease, cerebral palsy, diabetic neuropathy) 5.Subjects with rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including, but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome). Secondary Sjogren's syndrome or secondary limited cutaneous vasculitis within RA is permitted 6.Serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) within 3 months prior to D0 (V1/W0) 7.History of recurrent infections requiring oral or parental anti-infective drug treatment 8.Primary or secondary immunodeficiency (history of or currently active), including known history of HIV infection 9.History of tuberculosis or positive purified protein derivative (PPD; positive Mantoux test defined as >or=10 mm of induration [size of raised lump, not redness], or equivalent positive tuberculosis (TB) test result as per country clinical standards) during the screening period. When the PPD induration is >or=5 mm, but <10 mm the subject is eligible for the study if they have had a negative chest x-ray during the screening period. There must be no other clinical evidence of TB on physical examination of the subject. Note: Subjects who have had prior adequate prophylaxis treatment for latent TB with an appropriate course of isoniazid (INH) or equivalent, per country standards, are not excluded from study participation. 10.Fever (body temp. >38°C) or symptomatic viral infection or bacterial infection within 2 weeks prior to D0 11.Receipt of live vaccine within 4W prior to D0 12.Clinically significant chest x-ray abnormality at Screening (Note: chest x-ray is not required if one was performed within 3 months of D0) LAB. TESTS 13.Subjects with any laboratory test result at Screening considered clinically significant (as determined by the Investigator) or o AST or ALT >1.5 times than ULN established by the central laboratory o Platelet count <150,000/μL o Hemoglobin <8.5 g/dL o Neutrophils <1.5 x 10exp3/μL 14.Positive for hepatitis C antibody or hepatitis B [HBsAg, HbcAb, or HBsAb] at Screening. Refer to full protocol for additional clarification. TREATMENT HISTORY 15.Previous treatment with anti-TNF therapy or any other non-TNF inhibitor biologic or prosorba column for the treatment of RA 16.If subjects have previously received cell-depleting therapies (including, but not limited to, anti-CD3, anti-CD4, anti-CD5, anti-CD11a, anti-CD19, anti- CD22, and/or BlyS/BAFF),, relevant cell counts must have returned to normal 17.Treatment with another IMP within the 3 months prior to D0 or within 5 half-lives of the agent, whichever is longer 18.Previous exposure to BG9924 19.Treatment with the following concomitant medications as indicated below: o Any oral steroid exceeding 10 mg/day of prednisone or equivalent administered within 4 weeks prior to Day 0 or any oral steroid ≤10 mg/day of prednisone or equivalent that was not administered at a stable dose for at least 4 weeks prior to Day 0. o Leflunomide administered within 8 weeks prior to Day 0 (if the subject has received 11 days of standard cholestyramine or activated charcoal washout, treatment with leflunomide may not be administered within 14 days prior to Day 0). o Cyclosporin A administered within 6 months prior to Day 0. o Azathioprine or 6-MP administered within 28 days prior to Day 0. o Hydroxychloroquine sulfate or sulfasalazine (or equivalents), or any other allowed concomitant DMARDs, administered at doses greater than the recommended therapeutic dose or not administered at a stable dose for 4 weeks prior to Day 0. o Any NSAIDS not at a stable dose for least 2W prior to D0 o Intra-articular corticosteroid injections given within 4W prior to D0 20.Subjects who underwent any surgical procedure, including bone/joint surgery/synovectomy (including joint fusion or replacement), within 12W prior to D0 or who are planning an unapproved (by BIIB) procedure within 24 WKS of D0 MISCELLANEOUS 21. 22. 23. 24. 25. 26. and 27, refer to the study protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with an ACR50 response at Week 14 (Visit 8). |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |