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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01754935
First received: December 18, 2012
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: VX-509
Drug: VX-509 matching placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP]) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • ACR hybrid scores [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from baseline in the Physical Component and Mental Health Components of the SF-36 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: January 2013
Study Completion Date: February 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo Arm Drug: VX-509 matching placebo
0 mg oral tablet

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01754935

  Show 30 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Chair: Bradley Bloom, MD, FACR, FAAP Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01754935     History of Changes
Other Study ID Numbers: VX12-509-103, 2012-003439-41
Study First Received: December 18, 2012
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Estonia: The State Agency of Medicine
South Africa: Medicines Control Council
Lithuania: State Medicine Control Agency - Ministry of Health
Denmark: Danish Health and Medicines Authority
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014