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 evaluate the effects of 2 dosing regimens of VX-702 administered with concomitant methotrexate (MTX), and MTX alone, on the concentrations of serum and urinary biomarkers of inflammation and bone resorption. • To evaluate the safety and tolerability of VX-702 administered with concomitant MTX, and MTX alone, when administered for 12 weeks in subjects with moderate to severe rheumatoid arthritis (RA). |
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E.2.2 | Secondary objectives of the trial |
*To evaluate the effects of VX-702 on RA disease activity based on the 20% response as defined by the American College of Rheumatology criteria (ACR20) and the Disease Activity Score 28 (DAS28) as defined by the European League Against Rheumatism (EULAR). • To determine the pharmacokinetics (PK) and pharmacodynamics (PD) of VX-702 and MTX when administered concomitantly |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must be male or female, 18 to 75 years of age (inclusive) 2. Have a previously established diagnosis of RA as defined by the ACR revised criteria 3. Have active RA ≥ 6 months in duration as defined by the ACR revised criteria for RA with total disease duration >6 months and not exceeding 10 years 4. CRP ≥1.0 mg/dL 5. Have a swollen joint count of ≥6 out of 28 joints and tender joint count of ≥9 out of 28 joints. Joints that have had prior surgery are to be excluded from the joint count. 6. Must have been taking MTX for at least 6 months and have been on a stable dose of MTX 12.5 to 20 mg weekly for ≥4 weeks prior to Study Day 1. The MTX dose must remain stable throughout the study; unless downward modification is required for safety reasons. Change in the route of administration is not permitted during the study. 7. No concurrent DMARD treatment (other than a stable dose of MTX); DMARD treatment must have been discontinued ≥6 months prior to randomization 8. Subjects receiving a nonsteroidal antiinflammatory drug (NSAID) and/or prednisone (≤10 mg/day) must have been treated at a stable dose(s) for ≥ 1 month prior to randomization. Subjects may only be taking 1 NSAID. 9. All subjects must agree to use 2 methods of contraception, including 1 barrier method (i.e., a condom or diaphragm plus spermicide), during the treatment period and for 8 weeks after the completion of study drug (unless the subject is of documented non childbearing potential) 10. Female subjects must have a negative pregnancy test (β-hCG) at screening before the first dose of study drug 11. Must be an outpatient at the time of enrollment 12. Provide informed consent to participate in the study |
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E.4 | Principal exclusion criteria |
1. Pregnant women or nursing mothers 2. Male subjects with female partners that are pregnant, nursing, or planning to become pregnant during the study or within 30 days of the last dose of VX-702 3.Female subjects of childbearing potential who are not using adequate contraception (defined as use of a barrier method with spermicidal jelly or intrauterine device) 4. Have clinically significant abnormalities in prestudy clinical examination or in prestudy laboratory test results (including the presence of either hepatitis B surface antigen, hepatitis C virus antibody, or HIV antibody) 5. Requires use of medications that may interfere with study evaluations 6. Have any of the following concurrent medical conditions: • Uncontrolled diabetes or uncontrolled ischemic heart disease • Substantial renal impairment (creatinine clearance <40mL/min, calculated using the Cockcroft-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 • A prolongation of QTc interval (Fridericia correction), specifically QTc interval >450 ms in males or >480 ms in females • History of Torsade de Pointes or other significant arrhythmia or additional risk factors for Torsade de Pointes • Significant active infectious disease requiring systemic antimicrobial treatment, with the exception of uncomplicated bacterial cystitis in women • Evidence of tuberculosis on chest radiograph without documented adequate anti-TB treatment or known positive tuberculin skin test as follows: Subjects with ≥10 mm induration; unless completed adequate anti-TB prophylaxis documented prior to study entry and a negative chest radiograph within 6 months of study entry or unless BCG vaccination received and a negative chest radiograph within 6 months of study entry Subjects with >5mm and <10mm induration; unless a negative chest radiograph within 6 months of study entry or unless BCG vaccination received and a negative chest radiograph within 6 months of study entry • Any other concurrent condition which, in the opinion of the investigator, would preclude participation in or interfere with compliance with the protocol 7 Have elevation in liver function parameters at the Grade 1 toxicity level or higher (i.e., >1.5 x the upper limit of normal [ULN] for alanine aminotransferase [ALT], aspartate aminotransferase [AST], or total bilirubin) 8. Use of concomitant medications that are known to prolong the QTc interval 9. Have previously taken chlorambucil or cyclophosphamide 10. Have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1 11. Have undergone or are undergoing treatment with another investigational drug or approved treatment for investigational use within 1 month prior to randomization 12. Have planned major surgery (e.g., joint replacement) within the duration of the treatment period of the study 13. Have previously participated in any study with VX-702, unless duration of administration was ≤1 week and the subject did not discontinue from the study due to an AE |
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E.5 End points |
E.5.1 | Primary end point(s) |
•Biomarker response. Measured as the change from baseline in CRP, erythrocyte sedimentation rate (ESR), 55-kilodalton isoform soluble tumor necrosis factor receptor (sTNFRp55), and C terminal peptide Type-1 (CTX-1). • Safety and tolerability assessments |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 13 |