A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in Subjects With Rheumatoid Arthritis

A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in a Treat to Target Setting in Subjects With Rheumatoid Arthritis on Disease-Modifying Antirheumatic Drugs

This study is designed to evaluate the long-term safety and tolerability of VX-509 in subjects with active rheumatoid arthritis (RA) on DMARD therapy. This study will enroll subjects who completed a previous designated study with VX-509 (e.g., Study VX12-509-103).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: VX-509

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.

This study will follow a "treat to target" (T2T) paradigm. T2T strategies have been followed in non-rheumatologic fields for decades. T2T trials have been conducted for RA from the late 1990's, and have substantiated the concept that treating to a target is associated with a better outcome than standard of care treatment. This has led to recommendations by experts to use T2T strategies in clinical practice.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia
    • Vertex Investigational Site
• Lithuania
  • Vilnius, Lithuania
    • Vertex Investigational Site
• South Africa
  • Pretoria, South Africa
    • Vertex Investigational Site
  • Stellenbosch, South Africa
    • Vertex Investigational Site
• United States
  • California
    • 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
  • Kentucky
    • Elizabethtown, Kentucky, United States
      • Vertex Investigational Site
  • Maryland
    • Fredrick, 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
    • Greensboro, 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
    • Spokane, Washington, United States
      • Vertex Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have completed the assigned study drug treatment phase of a previous VX-509 study (e.g., Study 103).
• Subjects must voluntarily sign and date the Study 104 informed consent document.
• Subject must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other study procedures.

Exclusion Criteria:

• Inflammatory and rheumatological disorders other than RA, where arthritis may be a prominent feature.
• History of any clinically significant illness that might, in the opinion of the investigator, confound the results of the study or pose an additional risk in administering study drug(s) to the subject
• History of tuberculosis (TB), regardless of history of antimycobacterial treatment.
• Planned surgery during the study.
• History of alcohol or drug abuse, or excessive alcohol consumption as determined by the investigator, during the previous 12 months before Day 1.
• Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or planning to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm VX-509	Drug: VX-509; VX-509 dose may be increased every 8 weeks in a stepwise fashion from 100 to 150 mg and from 150 to 200 mg, as needed (determined by ongoing disease activity by CDAI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term safety and tolerability of VX-509 treatment	Measured by clinical laboratory tests	Baseline through 104 weeks
Long-term safety and tolerability of VX-509 treatment	Measured by adverse events (AEs)	Baseline through 104 weeks
Long-term safety and tolerability of VX-509 treatment	Measured by electrocardiograms (ECGs)	Baseline through 104 weeks
Long-term safety and tolerability of VX-509 treatment	Measured by vital signs	Baseline through 104 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects who achieve CDAI LDA (≤10) or CDAI remission (≤2.8)	Baseline through 104 weeks
Proportion of subjects who achieve ≥20% (50%, 70%) improvement in disease severity according to the ACR criteria, using CRP (ACR20 CRP, ACR50 CRP, ACR70 CRP)	Baseline through 104 weeks
Change from baseline in DAS28 using CRP (4-component) (DAS28 4[CRP])	Baseline through 104 weeks
Proportion of subjects with DAS28 4(CRP) <2.6 (DAS remission)	Baseline through 104 weeks
Proportion of subjects who achieve a moderate, good, or no response according to the EULAR response criteria from baseline	Baseline through 104 weeks
Percentage of subjects with decreased dose of DMARD and/or corticosteroid (if receiving), including the subsets with 50% withdrawal and with full withdrawal (dose = 0)	Baseline through 104 weeks
ACR hybrid scores	Baseline through 104 weeks
Proportion of subjects who achieve ACR20/50/70 with erythrocyte sedimentation rate (ESR) and DAS28 4(ESR) response from baseline	Baseline through 104 weeks
Proportion of subjects with DAS28 4(CRP) <3.2 (DAS LDA) from baseline	Baseline through 104 weeks
Proportion of subjects achieving a clinical remission (2011 ACR/EULAR criteria), including subsets achieving either the low joint count or simplified disease activity index (SDAI) score remission options (or both) from baseline	Baseline through week 104
Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)	Baseline through 104 weeks
Change from baseline in health-related quality of life assessed by 36-Item Short Form (SF 36) Physical Component Summary score and Physical Function (PF) subscale	Baseline through 104 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change in Outcome Measures in Rheumatology Clinical Trials (OMERACT) RAMRIS synovitis score, bone marrow edema (osteitis), erosion score, and joint space narrowing score by magnetic resonance imaging (MRI) in the designated hand	Baseline through week 12

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: April 10, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 12, 2013

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: October 23, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: VX12-509-104; 2012-004342-14 (EudraCT Number)