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

April 30, 2015 updated by: Vertex Pharmaceuticals Incorporated

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of VX-509 Using Magnetic Resonance Imaging and Arthroscopic Biopsies in Subjects With Active Rheumatoid Arthritis on Stable Disease-Modifying Antirheumatic Drugs

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Hillerød, Denmark
        • Vertex Investigational Site
      • Hjørring, Denmark
        • Vertex Investigational Site
  • Estonia
      • Tallinn, Estonia
        • Vertex Investigational Site
  • Lithuania
      • Vilnius, Lithuania
        • Vertex Investigational Site
  • Netherlands
      • Heerlen, Netherlands
        • Vertex Investigational Site
      • Utrecht, Netherlands
        • Vertex Investigational Site
  • South Africa
      • Johannesburg, South Africa
        • Vertex Investigational Site
      • Pretoria, South Africa
        • Vertex Investigational Site
      • Stellenbosch, South Africa
        • Vertex Investigational Site
  • United States
    • California
      • Stanford, California, United States
        • Vertex Investigational Site
      • Upland, California, United States
        • Vertex Investigational Site
    • Florida
      • Fort Lauderdale, Florida, United States
        • Vertex Investigational Site
      • Venice, Florida, United States
        • Vertex Investigational Site
      • West Palm Beach, Florida, United States
        • Vertex Investigational Site
    • Georgia
      • Canton, Georgia, United States
        • Vertex Investigational Site
      • Decatur, Georgia, United States
        • Vertex Investigational Site
    • Kansas
      • Kansas City, Kansas, United States
        • Vertex Investigational Site
    • Kentucky
      • Elizabethtown, Kentucky, United States
        • Vertex Investigational Site
    • Maryland
      • Frederick, Maryland, United States
        • Vertex Investigational Site
    • Nebraska
      • Lincoln, Nebraska, United States
        • Vertex Investigational Site
    • New York
      • Rochester, New York, United States
        • Vertex Investigational Site
    • North Carolina
      • Greenboro, North Carolina, United States
        • Vertex Investigational Site
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
        • Vertex Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • Vertex Investigational Site
    • Tennessee
      • Memphis, Tennessee, United States
        • Vertex Investigational Site
    • Texas
      • Katy, Texas, United States
        • Vertex Investigational Site
      • San Antonio, Texas, United States
        • Vertex Investigational Site
      • Webster, Texas, United States
        • Vertex Investigational Site
    • Washington
      • Seattle, Washington, United States
        • Vertex Investigational Site
      • Spokane, Washington, United States
        • Vertex Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Arm
Drug: VX-509 matching placebo
0 mg oral tablet
Experimental: VX-509 100 mg qd Arm
Drug: VX-509
50 mg oral tablet
Experimental: VX-509 200 mg qd Arm
Drug: VX-509
50 mg oral tablet
Experimental: VX-509 300 mg qd Arm
Drug: VX-509
50 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects achieving a ≥20% improvement in disease severity according to the American College of Rheumatology criteria (ACR20), using C reactive protein (CRP) (ACR20 CRP)
Time Frame: Week 12
Week 12
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist
Time Frame: Week 12
Week 12

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
Time Frame: Week 12
Week 12
Proportion of subjects with DAS28 CRP <2.6, and those who achieve a remission, moderate response or good response according to the European League Against Rheumatism (EULAR) response criteria
Time Frame: Week 12
Week 12
ACR hybrid scores
Time Frame: Week 12
Week 12
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
Time Frame: Week 6
Week 6
PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])
Time Frame: Week 12
Week 12
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Time Frame: Week 12
Week 12
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Time Frame: Week 12
Week 12
Change from baseline in the Physical Component and Mental Health Components of the SF-36
Time Frame: Week 12
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vertex Pharmaceuticals Incorporated

Investigators

  • Study Chair: Bradley Bloom, MD, FACR, FAAP, Vertex Pharmaceuticals Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

December 18, 2012

First Submitted That Met QC Criteria

December 18, 2012

First Posted (Estimate)

December 21, 2012

Study Record Updates

Last Update Posted (Estimate)

May 19, 2015

Last Update Submitted That Met QC Criteria

April 30, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX12-509-103
  • 2012-003439-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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