E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 long-term safety and tolerability of VX-509 treatment in subjects with RA on DMARD therapy |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of long-term VX-509 treatment in subjects with RA on DMARD therapy in a T2T paradigm, including induction of remission, LDA, major arthritis improvement, physical functioning, and ability to taper concurrent DMARD and corticosteroid (if receiving)
•To evaluate arthritis improvement with initial VX 509 treatment in subjects with RA on DMARD therapy who previously received no VX-509 treatment (placebo subjects)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects must have completed the assigned study drug treatment phase of a previous VX 509 study (e.g., Study 103).
2.Subjects must voluntarily sign and date the Study 104 informed consent document.
3.Subject must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.
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E.4 | Principal exclusion criteria |
1.Inflammatory and rheumatological disorders other than RA, where arthritis may be a prominent feature
2.History of any clinically significant illness that might, in the opinion of the investigator, confound the results of the study or pose an additional risk in administering study drug(s) to the subject.
3.History of cancer, except squamous or basal cell cancers of the skin or in situ cancer of the cervix.
4.History of hematologic disorders including neutropenia and thrombocytopenia other than Felty syndrome.
5.History of tuberculosis (TB), regardless of history of antimycobacterial treatment.
6.Acute or chronic active infection requiring systemic antimicrobial treatment with the exception of onychomycosis receiving antifungal medication or acne and rosacea receiving low-dose antibiotics.
7.History of previous osteomyelitis, infected joint, or joint prosthesis.
8.Subjects who are at high risk of developing an infection due to a compromised immune system including poorly controlled diabetes.
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E.5 End points |
E.5.1 | Primary end point(s) |
Long-term safety and tolerability of VX-509 treatment, as determined by adverse events (AEs), clinical laboratory tests, electrocardiograms (ECGs), and vital signs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Proportion of subjects who achieve CDAI LDA (≤10) or CDAI remission (≤2.8) from baseline over time
•Proportion of subjects who achieve ≥20% (50%, 70%) improvement in disease severity according to the ACR criteria, using CRP (ACR20 CRP, ACR50 CRP, ACR70 CRP) response from baseline over time
•Change from baseline in DAS28 using CRP (4-component) (DAS28 4[CRP]) over time
•Proportion of subjects with DAS28 4(CRP) <2.6 (DAS remission) from baseline over time
•Proportion of subjects who achieve a moderate, good, or no response according to the EULAR response criteria from baseline over time
•Percentage of subjects with decreased dose of DMARD and/or corticosteroid (if receiving), including the subsets with 50% withdrawal and with full withdrawal (dose = 0)
•ACR hybrid scores from baseline over time
•Proportion of subjects who achieve ACR20/50/70 with erythrocyte sedimentation rate (ESR) and DAS28-4(ESR) response from baseline over time
•Proportion of subjects with DAS28 4(CRP) <3.2 (DAS LDA) from baseline over time
•Proportion of subjects achieving a clinical remission (2011 ACR/EULAR criteria), including subsets achieving either the low joint count or SDAI remission options (or both) from baseline over time
•Change from baseline in Health Assessment Questionnaire – Disability Index (HAQ DI) over time
•Change from baseline in health-related quality of life assessed by 36-Item Short Form [SF-36]) Physical Component Summary (PCS) score and Physical Function (PF) subscale over time
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | No |
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 |
Denmark |
Estonia |
Lithuania |
Netherlands |
South Africa |
United States |
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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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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |