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

Rheumatoid Arthritis Clinical Trial

Official title:

A 12-week, Double-blind, Randomized, Parallel-group, Placebo-controlled Study of 4 Doses of VX-509 in Subjects With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01052194
• Other study ID #: VX09-509-101
• Secondary ID: 2009-017438-32
• Status: Completed
• Phase: Phase 2
• First received: January 18, 2010
• Last updated: December 12, 2012
• Start date: February 2010
• Est. completion date: July 2011

Study information

• Verified date: December 2012
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate safety and assess initial efficacy of VX-509, a JAK3 inhibitor, for treatment of subjects with active RA. This study will assess the clinical response of 4 doses of VX-509 compared to placebo when administered for 12 weeks to patients with active RA. The study will also evaluate the safety and tolerability of VX-509 compared to placebo when administered for 12 weeks to subjects with active RA.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
tablet, placebo b.i.d. for 12 weeks
• VX-509
tablets, 25mg b.i.d. for 12 weeks
• VX-509
tablet, 50 mg b.i.d. for 12 weeks
• VX-509
tablet, 100 mg b.i.d. for 12 weeks
• VX-509
tablet, 150 mg b.i.d. for 12 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Belgium,  Croatia,  Germany,  Hungary,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects who achieve an ACR20 response		Week 12	No
Primary	Change from baseline in DAS28		Week 12	No
Secondary	Proportion of subjects who achieve an ACR50,70 response		Week 12	No
Secondary	Proportion of subjects who achieve moderate or good EULAR response		Week 12	No
Secondary	Magnitude of improvement in the components of the ACR response criteria		Week 12	No
Secondary	Pharmacokinetics of VX-509		Week 6	No
Secondary	Pharmacodynamics (PD) of biomarker responses		Week 6	No