A 12-week Study of 4 Doses of VX-509 in Subjects With Active Rheumatoid Arthritis

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 206

Inclusion Criteria

All subjects must have been diagnosed with RA as defined by the ACR revised criteria with disease duration of at least 6 months from confirmed diagnosis
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.
Baseline CRP level must be 1.5 times greater than the upper limit of normal at Screening.
Subjects must have failed at least 1 nonbiologic DMARD for any reason.
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.
Subjects must be willing to comply with contraception requirements.

Exclusion Criteria

Subjects with inflammatory rheumatological disorders other than RA.
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.
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 -- Subjects with elevation in alanine aminotransferase or aspartate aminotransferase above the upper limit of normal.
History of hematologic disorders including neutropenia and thrombocytopenia.
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.
Subjects who require concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A.
Subjects who have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1.
Subjects who have planned major surgery (e.g., joint replacement) or any procedures during the study.
Have received any live, attenuated vaccinations within 1 month prior to study drug administration.
History of drug or alcohol abuse or excessive alcohol as determined by the investigator, during the last 12 months before the screening visit.
History of TB infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
150 mg b.i.d. VX-509	VX-509	-
100 mg b.i.d. VX-509	VX-509	-
50 mg b.i.d. VX-509	VX-509	-
25 mg b.i.d. VX-509	VX-509	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change from baseline in DAS28	Week 12
Proportion of subjects who achieve an ACR20 response	Week 12

Secondary Outcome Measures

Name	Time	Method
Magnitude of improvement in the components of the ACR response criteria	Week 12
Proportion of subjects who achieve an ACR50,70 response	Week 12
Proportion of subjects who achieve moderate or good EULAR response	Week 12
Pharmacodynamics (PD) of biomarker responses	Week 6
Pharmacokinetics of VX-509	Week 6