E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 define the clinical response to placebo and two doses of VX-702 in subjects with RA using the number of 20% responses as defined by the American College of Rheumatology (ACR20) at Week 12 by applying the Jonckheere-Terpstra trend analysis - To evaluate the safety and tolerability of 2 dose levels of VX-702 compared to placebo, when administered for 12 weeks to subjects with RA |
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E.2.2 | Secondary objectives of the trial |
- To define the clinical response to placebo and two doses of VX-702 in subjects with RA using the ACR defined 50% and 70% responses (ACR50, 70) over a 12-week treatment period by applying the Jonckheere-Terpstra trend analysis - To compare the ACR20 response of individual VX-702 dose groups versus the placebo group at 12 weeks, by applying pair-wise comparisons - To define the clinical response to placebo and two doses of VX-702 in subjects with RA by using the sum of ranks of individual components of the ACR assessment and the maximum improvements in ACR assessment observed during treatment, by applying the Jonckheere-Terpstra trend analysis - To determine the PK and pharmacodynamics (PD) of VX-702 when administered to subjects with RA for 12 weeks |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Eighteen to 75 years of age 2. Active RA of ≥6 months in duration as defined by the ACR revised criteria for RA 3. CRP (>2 mg/dL) at the time of randomization 4. Swollen joint count of ≥8 of 28 and tender joint count of ≥10 of 28. Joints that have had prior surgery are to be excluded from the joint count. 5. No prior treatment with DMARD therapy (i.e., DMARD naive) or inadequate response to DMARD therapy. (Disease modifying anti-rheumatic drugs include oral or injectable gold, penicillamine, hydroxychloroquine, sulfasalazine, methotrexate, or leflunomide, please consult the product label for wash out period of leflunomide ). If the subject has received prior DMARD therapy with an antibody or binding protein to TNF (anti-TNF), or with recombinant IL-1 receptor antagonist (IL-1Ra), he/she may have discontinued treatment because of tolerability reasons, but may not have discontinued treatment because of an inadequate response. Cyclosporin therapy should have been discontinued for a minimum of 6 month prior to entry into the study 6. If the subject has received treatment with ≤3 DMARDs, he/she must have discontinued DMARD therapy (except for sulfasalazine or hydroxychloroquine) ≥1 month prior to randomization. Subjects who are receiving a stable dose of sulfasalazine or hydroxychloroquine for 30 days prior to randomization can remain on these drugs during the study. Subjects can be switched from another therapy to sulfasalazine or hydroxychloroquine and be eligible for the study after 1 month at a stable dose. Subjects must not receive leflunomide or injectable gold for ≥6 months prior to randomization, unless an appropriate washout procedure was carried out (leflunomide). 7. Subjects receiving a nonsteroidal anti-inflammatory drug (NSAID, only one allowed) and/or prednisone (≤10 mg/day) must have been treated at a stable dose(s) for ≥1 month prior to randomization. 8. Provide informed consent to participate in the study |
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E.4 | Principal exclusion criteria |
1. Pregnant women or nursing mothers 2. Female subject of childbearing potential who is not using adequate contraception (defined as use of a barrier method with spermicidal jelly or intrauterine device) 3. Requires concurrent DMARD therapy (other than sulfasalazine or hydroxychloroquine) 4. Has clinically significant abnormalities in prestudy clinical examination or in prestudy laboratory test results (including the presence of either hepatitis B surface antigen or hepatitis C antibody) 5. Requires use of medications that may interfere with study evaluations 6. Has any of the following concurrent medical conditions: - Uncontrolled diabetes or uncontrolled ischemic heart disease − Substantial renal impairment (creatinine clearance <40 mL/min, calculated using the Cockroft-Gault formula) − History of cancer (with the exception of basal or squamous cell carcinoma of the skin if adequately treated and no recurrence for >3 years) − History of liver disease − History of Torsade de Point and other significant arrhythmia − Significant active infectious disease requiring systemic antimicrobial therapy, with the exception of uncomplicated bacterial cystitis in women − Known positive tuberculin skin test or evidence of tuberculosis by chest X-ray, without adequate treatment (please consult Appendix I for details) − Any other concurrent condition which, in the opinion of the investigator, would preclude participation in or interfere with compliance with the protocol 7. Has elevation in liver function parameters at the Grade 1 toxicity level or higher (i.e., >1.5 × the ULN for ALT, AST, or total bilirubin) 8. Has undergone or is undergoing treatment with another investigational drug or approved therapy for investigational use within 1 month prior to randomization 9. Has previously participation in this study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is the ACR20 response at Week 12. An ACR20 response is defined by the following: • Improvement (reduction) by ≥20% from baseline in the absolute number of both swollen and tender joints, and • Improvement by ≥20% from baseline in ≥3 of the following evaluations: − Physician and subject global assessments of disease − Subject assessment of pain by visual analog scale (VAS) − Subject self-assessment of disability (Health Assessment Questionnaire [HAQ]) − Acute phase response as measured by laboratory tests (erythrocyte sedimentation rate [ESR] or C-reactive protein [CRP]). |
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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 | 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 | 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 | 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 | Information not present in EudraCT |
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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Last subject completing follow-up visit. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
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 | 0 |