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 Day 0. 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 = 28mm/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 (S) body weight <50kg 2. S hist of malignancy/ carcinoma in situ (S with hist of excised or treated basal cell carcinoma are eligible to participate in this study) 3.S 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.Hist of clin sign (as det by Inv) 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.S with rheumatic autoimmune disease other than RA, or sign syst involvement sec to RA (incl, but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome). Sec Sjogren's syndrome or secondary limited cutaneous vasculitis within RA is permitted 6.Serious local infection (e.g. cellulitis, abscess) or syst inf (e.g. pneumonia, septicemia) within 3M prior to D0 (V1/W0) 7.Hist of recurrent inf requiring oral/parental anti-inf drug treatment 8.Prim/sec immunodef (history of/currently active), including history of HIV infection 9.History of TB or pos purified protein derivative (PPD; pos Mantoux test >or=10 mm of induration [size of raised lump, not redness], or equivalent positive TB test result as per country clin standards) during the screening period. When PPD induration is >or=5 mm, but <10 mm the S is eligible for study if they have had a negative chest x-ray during the screening period. There must be no other clin evidence of TB on physical examination of the S. Note: S who have had prior adequate prophylaxis treatment for latent TB with an appropriate course of isoniazid (INH) or eq, per country standards, are not excl from study participation. 10.Fever (body temp. >38°C) or sympt viral infor bact inf within 2W prior to D0 11.Receipt of live vaccine within 4W prior to D0 12.Clin sign chest x-ray abnormality at Screening (Note: chest x-ray not required if one perf within 3M of D0) LAB. TESTS 13.S with any lab test result at Screening considered clin sign (as determined by the Inv) or o AST or ALT >1.5 times than ULN established by the central lab o Platelet count <150,000/μL o Hemoglobin <8.5 g/dL o Neutrophils <1.5 x 10exp3/μL 14.Pos hepatitis C Ab/hepatitis B [HBsAg, HbcAb/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 S have previously received cell-depleting therapies (incl, but not limited to, anti-CD3, anti-CD4, anti-CD5, anti-CD11a, anti-CD19, anti-CD22, and/or BlyS/BAFF), rel cell counts must have returned to normal 17.Treatment with another IMP within the 3M prior to D0 or within 5 half-lives of the agent, whichever is longer 18.Previous exposure to BG9924 19.Treatment with following concomitant medications: o Any oral steroid exceeding 10 mg/day of prednisone/eq adm within 4W prior to D0 or any oral steroid < or = 10mg/D of prednisone or eq that was not administered at a stable dose for at least 4W prior to D0 o Leflunomide adm within 8W prior to D0 (if S received 11D of stand cholestyramine/activated charcoal washout, treatment with leflunomide may not be adm within 14D prior D0) o Cyclosporin A adm within 6M prior to D0 o Azathioprine or 6-MP adm within 28D prior to D0 o Hydroxychloroquine sulfate or sulfasalazine (or equivalents), or any other allowed concomitant DMARDs, adm at doses greater than the recommended therapeutic dose or not administered at a stable dose for 4W prior to D0 o Any NSAIDS not adm at a stable dose for least 2W prior to D0 o IA corticosteroid inj within 4W prior to D0 20.S who underwent any surgical proc, incl bone/joint surgery/synovectomy (including joint fusion or replacement), within 12W prior to D0 or who are planning an unapproved (by BIIB) proc within 24 WKS of D0 MISCELLANEOUS 21.Nursing mothers, pregnant women, or women who are planning to become pregnant while in the study 22.Male and female subjects of childbearing potential not willing to practice effective birth control for the duration of the study. Female S must be: (1) postmenopausal for at least 12 months, (2) surgically sterile, or (3) willing to use 2 documented forms of birth control (e.g. barrier and spermicide, intrauterine device and barrier or spermicide, or birth control pill and barrier or spermicide) 23.Blood donation (1 unit or more) within 1 month prior to Screening 24.History of drug or alcohol abuse (as determined by the Inv) within 1Y prior to D0 25.Current enrollment in any other IMP study 26.Previous participation in this study 27.S expected to be unavailable for duration of trial, likely to be noncompliant with protocol, or who are felt to be unsuitable by Inv/Sponsor for any other reason |
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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.8.4.1 | 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 | 24 |
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 | 1 |
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 |