A Magnetic Resonance Imaging Study and Arthroscopic Biopsy Substudy in Subjects With Active Rheumatoid Arthritis Receiving VX-509, an Oral JAK3 Inhibitor

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: VX-509; Drug: VX-509 matching placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01754935

VX12-509-103

2012-003439-41 (EudraCT Number)

Details and patient eligibility

About

The current study is designed to evaluate the safety and efficacy, including MRI imaging, across a range of VX-509 doses in subjects with active rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs).

Full 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.

Enrollment: 43 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female subjects 18 to 65 years of age (inclusive)
• Diagnosis of RA
• Swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
• Seropositivity based on either a positive rheumatoid factor or anti cyclic citrullinated peptide antibody at screening -OR- known erosive disease based on previous X-ray report or erosions detected on screening hand and foot X-ray
• Baseline CRP level or Westergren erythrocyte sedimentation rate ≥1.2 × upper limit of normal
• Receiving stable therapy with 1 of the following DMARDs: methotrexate, sulfasalazine, leflunomide, anti-malarial drug, or penicillamine
• Palpable 2+ synovitis of the wrist or ≥2 MCPs in the MRI-designated hand

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.
• Inflammatory, rheumatological disorders other than RA, where arthritis may be a prominent feature
• Planned surgery during the study
• History of alcohol or drug 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.
• Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or planning to become pregnant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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43 participants in 4 patient groups, including a placebo group

VX-509 100 mg qd Arm

Experimental group

Treatment:

Drug: VX-509

VX-509 200 mg qd Arm

Experimental group

Treatment:

Drug: VX-509

VX-509 300 mg qd Arm

Experimental group

Treatment:

Drug: VX-509

Placebo Arm

Placebo Comparator group

Treatment:

Drug: VX-509 matching placebo