E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
active rheumatoid arthritis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
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 |
• To assess the clinical response of 4 doses of VX-509 compared to placebo in subjects with active RA as defined by 2 endpoints: the American College of Rheumatology defined 20% response (ACR20) and the change from baseline using Disease Activity Score (DAS)28 improvement at Week 12
• To evaluate the safety and tolerability of VX-509 compared to placebo when administered for 12 weeks to subjects with active RA
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E.2.2 | Secondary objectives of the trial |
• To assess the clinical response of 4 doses of VX-509 compared to placebo in subjects with active RA using the following: o ACR-defined 50% and 70% responses (ACR50,70) over a 12-week treatment period o EULAR (European League against Rheumatism) response over a 12-week treatment period • To assess the improvement in individual components of the ACR response of 4 doses of VX-509 compared to placebo over a 12-week treatment period • To determine the pharmacokinetics (PK) of VX-509 when administered to subjects with active RA for 12 weeks • To assess the phosphorylated signal transducer and activator of transcription (P-STAT) biomarker responses in blood and inflammatory protein/proteomic biomarker responses in plasma • To assess the magnitude of improvement in quality of life (Short Form-36 [SF-361)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects, between 18 and 75 years of age (inclusive) on the date of consent who agree on study participation and are able to read, understand, and sign and date a written ICF. 2. All subjects must have been diagnosed with RA as defined by the ACR revised criteria (Appendix A), with disease duration of at least 6 months from confirmed diagnosis. 3. Subjects must have a swollen joint count of ≥ 6 out of 28 joints and tender joint count of ≥6 out of 28 joints. Joints that have had prior surgery are to be excluded from the joint count. 4. Baseline CRP level must be 1.5 times greater than the upper limit of normal at Screening. 5. Subjects must have failed at least 1 nonbiologic DMARD for any reason (please refer to Appendix B for a list of DMARDs). Subjects who have failed previous treatment with MTX must have at least a 1 -month washout period since the last dose of MTX prior to Day 1. Washout periods for other DMARDs are listed in Appendix B. 6. Subjects may have previously failed no more than 1 biologic DMARD and discontinued treatment for reasons other than inadequate response. Subjects must not have been treated with Rituximab previously. Required washout period from previous biologic DMARD is at least 60 days. 7. Females must have a negative serum pregnancy test at the screening visit and also a negative urine pregnancy test at the screening visit and on Day 1 prior to study dosing. Male subjects must be willing to comply with contraception requirements as outlined in Section 12.5.5.1. 8. Sexually active subjects and their partners must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], or intrauterine devices [IUDs]) during the course of the study and for 3 months following discontinuation of study treatments (excluding women who are not of childbearing potential and men who have been sterilized). Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings) should not be used as a medically accepted method of contraception on this study. 9. Subjects must agree not to participate in other interventional clinical studies for the duration of their participation in this trial. 10. Subjects able to understand and be willing to comply with protocol requirements and instructions and likely to complete the study as planned. |
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E.4 | Principal exclusion criteria |
1. Subjects with inflammatory rheumatological disorders other than RA, where arthritis may be a prominent feature, such as systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polydermatomyositis, or Sjogren syndrome, will be excluded. Subjects with RA who have conditions associated secondarily with RA (e.g., osteoarthritis of affected joint[s] or sicca syndrome) may be considered for enrollment. 2. Female subject who is pregnant or nursing. 3. Male subjects with female partners that are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last dose of VX-509. 4. History or evidence of a clinically significant disorder other than RA (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric disorders), condition or disease that, in the opinion of the investigator and medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. 5. Subjects with clinically important abnormalities in screening physical examination or in screening laboratory test results (including the presence of either hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 and 2 antibody). 6. Subjects with elevation in alanine aminotransferase or aspartate aminotransferase above the upper limit of normal. 7. History of hematologic disorders including neutropenia and thrombocytopenia. 8. Subjects with an acute or chronic active infection requiring systemic antimicrobial treatment, or subjects who are at high risk of developing an infection due to a compromised immune system. Antifungals for onychomycosis or low-dose antibiotics for rosacea, that are not inhibitors or inducers of CYP3A, will be allowed. 9. Subjects who have undergone or are undergoing treatment with another investigational drug or approved treatment for investigational use within 3 months or 5 half-lives of the drug, whichever is greater. 10. Subjects who require concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A. Please refer to Appendix C for a partial list of such medications. 1 1. Subjects who have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1. 12. Subjects who have planned major surgery (e.g., joint replacement) or any procedures during the study. 13. Have received any live, attenuated vaccinations within 1 month prior to study drug administration. Note: Subjects who receive study drug should not receive any type of these vaccinations within 1 month after receiving their final dose. 14. History of drug or alcohol abuse or excessive alcohol as determined by the investigator, during the last 12 months before the screening visit. 15. History of TB infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment. Subjects must be screened for TB by customary clinical measures (history, chest x-ray, and skin test) at Screening. Subjects with a PPD skin test with induration >5 mm and <10 mm must have: 1) a negative screening chest radiograph at Screening, 2) a history of Bacille Calmette-Guérin (BCG) vaccination, and 3) a negative serologic test for TB (such as the QuantiFERON or T-spot TB test) in order to be considered eligible for study entry. Subjects with a PPD test 10 mm or greater induration are excluded regardless of BCG vaccination history. |
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E.5 End points |
E.5.1 | Primary end point(s) |
o Proportion of subjects who achieve an ACR20 response at Week 12 o Change from baseline in DAS28 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | 22 |
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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The end of the study is defined as the date of final database lock |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |