Clinical trial NCT01830985: A Phase 2/3 Open-label Extension Study to Evaluate Long-Term Safety and Efficacy With VX-509 in Subjects With Rheumatoid Arthritis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2013-04-12
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Long-term safety and tolerability of VX-509 treatment
timeFrame: Baseline through 104 weeks
measure: Long-term safety and tolerability of VX-509 treatment
timeFrame: Baseline through 104 weeks
measure: Long-term safety and tolerability of VX-509 treatment
timeFrame: Baseline through 104 weeks
measure: Long-term safety and tolerability of VX-509 treatment
timeFrame: Baseline through 104 weeks
Secondary outcomes:
measure: Proportion of subjects who achieve CDAI LDA (≤10) or CDAI remission (≤2.8)
timeFrame: Baseline through 104 weeks
measure: 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)
timeFrame: Baseline through 104 weeks
measure: Change from baseline in DAS28 using CRP (4-component) (DAS28 4[CRP])
timeFrame: Baseline through 104 weeks
measure: Proportion of subjects with DAS28 4(CRP) <2.6 (DAS remission)
timeFrame: Baseline through 104 weeks
measure: Proportion of subjects who achieve a moderate, good, or no response according to the EULAR response criteria from baseline
timeFrame: Baseline through 104 weeks
measure: 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)
timeFrame: Baseline through 104 weeks
measure: ACR hybrid scores
timeFrame: Baseline through 104 weeks
measure: Proportion of subjects who achieve ACR20/50/70 with erythrocyte sedimentation rate (ESR) and DAS28 4(ESR) response from baseline
timeFrame: Baseline through 104 weeks
measure: Proportion of subjects with DAS28 4(CRP) <3.2 (DAS LDA) from baseline
timeFrame: Baseline through 104 weeks
measure: 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
timeFrame: Baseline through week 104
measure: Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)
timeFrame: Baseline through 104 weeks
measure: 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
timeFrame: Baseline through 104 weeks
Other outcomes:
measure: 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
timeFrame: Baseline through week 12
Locations:
city: Upland
country: United States
facility: Vertex Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: Vertex Investigational Site
state: Florida
city: Venice
country: United States
facility: Vertex Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: Vertex Investigational Site
state: Florida
city: Canton
country: United States
facility: Vertex Investigational Site
state: Georgia
city: Decatur
country: United States
facility: Vertex Investigational Site
state: Georgia
city: Elizabethtown
country: United States
facility: Vertex Investigational Site
state: Kentucky
city: Fredrick
country: United States
facility: Vertex Investigational Site
state: Maryland
city: Lincoln
country: United States
facility: Vertex Investigational Site
state: Nebraska
city: Rochester
country: United States
facility: Vertex Investigational Site
state: New York
city: Greensboro
country: United States
facility: Vertex Investigational Site
state: North Carolina
city: Duncansville
country: United States
facility: Vertex Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Vertex Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Vertex Investigational Site
state: Tennessee
city: Katy
country: United States
facility: Vertex Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Vertex Investigational Site
state: Texas
city: Webster
country: United States
facility: Vertex Investigational Site
state: Texas
city: Spokane
country: United States
facility: Vertex Investigational Site
state: Washington
city: Tallinn
country: Estonia
facility: Vertex Investigational Site
city: Vilnius
country: Lithuania
facility: Vertex Investigational Site
city: Pretoria
country: South Africa
facility: Vertex Investigational Site
city: Stellenbosch
country: South Africa
facility: Vertex Investigational Site
Study officials:
affiliation: Vertex Pharmaceuticals Incorporated
name: Bradley Bloom, MD, FACR, FAAP
role: STUDY_CHAIR
References: