24-week Study With Open Label Extension of VX-509, an Oral JAK3 Inhibitor, in Subjects Taking Methotrexate

Phase 2

Completed

Brief Summary: This study is designed to evaluate the safety and efficacy of VX-509, an oral JAK3 inhibitor, for treatment of subjects with active RA who have had an inadequate response to Methotrexate.

Detailed Description: 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, and a broad range of other autoimmune diseases.

Recruitment & Eligibility

Inclusion Criteria

Male and female subjects, between 18 and 80 years of age (inclusive)
All subjects must have been diagnosed with RA
Must have a swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
Baseline CRP level must be above the upper limit of normal
All subjects must have been receiving stable MTX coadministered with folic or folinic acid (at least 5 mg/week)
Subjects may remain on 1 nonsteroidal anti-inflammatory medication during the study (aspirin ≤ 325 mg/day is allowed).
Subjects must not have received prior treatment with a JAK inhibitor
Subjects who are on an additional nonbiologic DMARD (e.g., sulfasalazine) must be willing to discontinue that DMARD after signing consent, except for hydroxychloroquine
Subjects may have received previous therapy with a single TNF inhibitor (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol)
Females must have a negative pregnancy test prior to study dosing
Sexually active subjects and their partners must agree to contraceptive requirements

Exclusion Criteria

History or presence of a clinically significant medical disorder other than RA 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.
Subjects with inflammatory, rheumatological disorders other than RA
Pregnant or nursing female subjects
Subjects who have a female partner who is pregnant, nursing, or planning to become pregnant
Subjects who have planned major surgery (e.g., joint replacement) or procedures during the study
History of drug abuse or positive drug screen
History of alcohol abuse or excessive alcohol consumption
History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Proportion of subjects who achieve a 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP) response	Week 12
Safety and tolerability	Week 12	Measured by vital signs
Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)	Week 12

Secondary Outcome Measures

Name	Time	Method
Proportion of subjects who achieve an ACR20-CRP response	Week 24
Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses	Week 12 and 24
Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria	Week 12 and 24
Proportion of subjects who achieve remission as defined by DAS28-CRP response	Week 12 and 24
Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission	Week 12 and 24
Change from baseline in selected Patient Reported Outcomes (PROs)	Week 12 and 24
Change from baseline in DAS28- CRP	Week 24
Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs	Week 24