A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in Subjects With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study is designed to evaluate the long-term safety and tolerability of VX-509 in subjects with active rheumatoid arthritis (RA) on DMARD therapy. This study will enroll subjects who completed a previous designated study with VX-509 (e.g., Study VX12-509-103).

Detailed Description
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VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This cascade ultimately contributes to abnormal immune response that results in chronic inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the treatment of RA. This study will follow a treat to target (T2T) paradigm. T2T strategies have been followed in non-rheumatologic fields for decades. T2T trials have been conducted for RA from the late 1990's, and have substantiated the concept that treating to a target is associated with a better outcome than standard of care treatment. This has led to recommendations by experts to use T2T strategies in clinical practice.

Official Title
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A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in a Treat to Target Setting in Subjects With Rheumatoid Arthritis on Disease-Modifying Antirheumatic Drugs

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: VX-509


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed the assigned study drug treatment phase of a previous VX-509 study (e.g., Study 103). Subjects must voluntarily sign and date the Study 104 informed consent document. Subject must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures. Exclusion Criteria: Inflammatory and rheumatological disorders other than RA, where arthritis may be a prominent feature. 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 History of tuberculosis (TB), regardless of history of antimycobacterial treatment. Planned surgery during the study. History of alcohol or drug abuse, or excessive alcohol consumption as determined by the investigator, during the previous 12 months before Day 1. Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or planning to become pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm VX-509<br> | Drug: VX-509<br>* VX-509 dose may be increased every 8 weeks in a stepwise fashion from 100 to 150 mg and from 150 to 200 mg, as needed (determined by ongoing disease activity by CDAI)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term safety and tolerability of VX-509 treatment | Measured by clinical laboratory tests | Baseline through 104 weeks | 
| Long-term safety and tolerability of VX-509 treatment | Measured by adverse events (AEs) | Baseline through 104 weeks | 
| Long-term safety and tolerability of VX-509 treatment | Measured by electrocardiograms (ECGs) | Baseline through 104 weeks | 
| Long-term safety and tolerability of VX-509 treatment | Measured by vital signs | Baseline through 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve CDAI LDA (≤10) or CDAI remission (≤2.8) |  | Baseline through 104 weeks | 
| 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) |  | Baseline through 104 weeks | 
| Change from baseline in DAS28 using CRP (4-component) (DAS28 4[CRP]) |  | Baseline through 104 weeks | 
| Proportion of subjects with DAS28 4(CRP) <2.6 (DAS remission) |  | Baseline through 104 weeks | 
| Proportion of subjects who achieve a moderate, good, or no response according to the EULAR response criteria from baseline |  | Baseline through 104 weeks | 
| 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) |  | Baseline through 104 weeks | 
| ACR hybrid scores |  | Baseline through 104 weeks | 
| Proportion of subjects who achieve ACR20/50/70 with erythrocyte sedimentation rate (ESR) and DAS28 4(ESR) response from baseline |  | Baseline through 104 weeks | 
| Proportion of subjects with DAS28 4(CRP) <3.2 (DAS LDA) from baseline |  | Baseline through 104 weeks | 
| Proportion of subjects achieving a clinical remission (2011 ACR/EULAR criteria), including subsets achieving either the low joint count or simplified disease activity index (SDAI) score remission options (or both) from baseline |  | Baseline through week 104 | 
| Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) |  | Baseline through 104 weeks | 
| Change from baseline in health-related quality of life assessed by 36-Item Short Form (SF 36) Physical Component Summary score and Physical Function (PF) subscale |  | Baseline through 104 weeks |