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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01590459

2011-004419-22 (EudraCT Number)

VX11-509-102

Details and patient eligibility

About

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.

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: 359 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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359 participants in 5 patient groups, including a placebo group

Placebo Arm

Placebo Comparator group

Treatment:

Drug: VX-509 matching placebo

VX-509 100 mg qd Arm

Experimental group

Treatment:

Drug: VX-509

VX-509 150 mg qd Arm

Experimental group

Treatment:

Drug: VX-509

VX-509 100 mg bid Arm

Experimental group

Treatment:

Drug: VX-509

VX-509 200 mg qd Arm

Experimental group

Treatment:

Drug: VX-509