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 |
The primary objective of this study is to evaluate the clinical efficacy of BG00012 with MTX in subjects with active RA who have had an inadequate response to DMARD therapy. |
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E.2.2 | Secondary objectives of the trial |
To determine the safety and tolerability of BG00012 with MTX in this 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 |
A PK/PD sub-study is included in the main protocol 109RA201 Version 4.2 dated 10 February 2009. Objectives related to the sub-study To assess the pharmacokinetic (PK) profile of BG00012 and its relationship to selected PD parameters. To assess the effects of genetic and genomic determinants on BG00012 PK, PD and efficacy parameters. |
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E.3 | Principal inclusion criteria |
1. Must give written informed consent and any authorisations required by local law 2. Aged 18-75 years old inclusive at time of randomisation 3. Must have a diagnosis of adult, onset RA according to the 1987 Revised American Rheumatism Association Criteria for the Classification of Rheumatoid Arthritis (Section 22, Appendix A1), and be (Function Class I-III) (Section 22, Appendix A2), for at least 6 months prior to Day 0 4.Must have been treated with and be tolerating MTX (≥7.5 mg/week to ≤ 25 mg/week) for at least three months immediately prior to Day 0 5. Must have had an inadequate response to at least 1 coventional DMARD therapy (e.g. MTX, leflunomide, sulfasalazine, etc.) due to inadequate efficacy or toxicity 6.Must have a swollen joint count (SJC) ≥6 and a Tender Joint Count (TJC) ≥6 (66/68 joint count at screening) 7. Must have an elevated hsCRP ≥ 1.5 times the upper limit of normal (ULN) or erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr at Screening 8.Must be willing to receive oral folate (≥ 5mg/week) or folinic acid (≥1mg/week) for the duration of the study 9. All male and female subjects of child-bearing potential must practice effective contraception during the study and be willing and able to continue contraception for 1 month after their last dose of study treatment |
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E.4 | Principal exclusion criteria |
1. Subjects with a history of malignant disease, including solid tumours and haematologic malignancies (except basal cell and squamous cell carcinomas of the skin that have been completed excised and are considered cured) 2. History of severe allergic or anaphylactic reactions or known drug hypersensitivity. 3. History of clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal or haematologic insufficiency, or any major disease that could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinson's Disease, cerebal palsy, diabetic neuropathy) 4. Known active bacterial, viral, fungal, mycobacterial, opportunistic infection or other infection (including atypical micobacterial disease, but excluding fungal infections of the nail beds) or any major episode of infection requiring hospitalisation or treatment with intravenous (IV) antibiotics within 4 weeks of Day 0 5. Nursing mothers, pregnant women, or women who are planning to become pregnant while in the study 6 Treatment with another investigational drug, investigational device, or approved therapy for investigational use within three months prior to Day 0 or within 5 half-lives of the agent, whichever is longer. 7. Previous treatment with anti-TNF treatment or any other non-TNF inhibitor biologic or prosorba column 8. Any live immunisation/vaccination within 1 month prior to dosing. 9. Treatment with the following concomitant medications: - 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 equvalent that was not administered at a stable dose for at least 4 weeks prior to Day 0 - Leflunomide administered within 8 weeks prior to Day 0 - Cyclosporin A administered within 8 weeks prior to Day 0 - Azathioprine or 6-MP administered within 28 days prior to Day 0 -Hydroxychloroquine sulfate or sulfasalazine, or any other allowed concomitant DMARDS administered at doses greater than the recommended therapeutic dose or not adminstered at a stable dose for 4 weeks prior to Day 0 - Any NSAIDS not administered at a stable dose for at least 2 weeks prior to Day 0 - Intra-articular or intramuscular corticosteroid injections given within 4 weeks prior to Day 0 10. Previous exposure to BG00012 or FUMADERM® for RA 11. Subjects who underwent any surgical procedure, including bone, joint, synovectomy within 12 weeks prior to Day 0 or who are planning unapproved ( by Biogen Idec) procedure within 16 weeks prior to Day 0 12. Subjects with any laboratory test result at screening visit considered clinically significant 13. Serum creatinine > 1.2 ULN established by the central laboratory 14. Any of the following abnormal urine tests at screening, confirmed by a second urinalysis 2 weeks later: -proteinuria (1+ or greater) - haematuria, without known etiology - glycosuria, without known etiology 15. Positive for hepatitis C or current hepatitis B infection 16. Known to be postive for HIV at screening visit 17. Blood donation within 2 months prior to Day 0 18. History of drug or alcohol abuse within 1 year prior to Day 0 19. Current enrollment in any other study treatment or disease study 20.Inability to comply with study requirements 21. Other unspecified reasons that, in the opinion of the investigator or Biogen Idec, make the subject unsuitable for enrollment
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of subjects with ACR20 response at week 12 |
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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 | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |