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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01830985
• Other study ID #: VX12-509-104
• Secondary ID: 2012-004342-14
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 10, 2013
• Last updated: October 23, 2015
• Start date: April 2013
• Est. completion date: July 2014

Study information

• Verified date: October 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardEstonia: The State Agency of MedicineSouth Africa: Medicines Control CouncilLithuania: State Medicine Control Agency - Ministry of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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)

Locations

Country	Name	City	State
Estonia	Vertex Investigational Site	Tallinn
Lithuania	Vertex Investigational Site	Vilnius
South Africa	Vertex Investigational Site	Pretoria
South Africa	Vertex Investigational Site	Stellenbosch
United States	Vertex Investigational Site	Canton	Georgia
United States	Vertex Investigational Site	Charleston	South Carolina
United States	Vertex Investigational Site	Decatur	Georgia
United States	Vertex Investigational Site	Duncansville	Pennsylvania
United States	Vertex Investigational Site	Elizabethtown	Kentucky
United States	Vertex Investigational Site	Fort Lauderdale	Florida
United States	Vertex Investigational Site	Fredrick	Maryland
United States	Vertex Investigational Site	Greensboro	North Carolina
United States	Vertex Investigational Site	Katy	Texas
United States	Vertex Investigational Site	Lincoln	Nebraska
United States	Vertex Investigational Site	Memphis	Tennessee
United States	Vertex Investigational Site	Rochester	New York
United States	Vertex Investigational Site	San Antonio	Texas
United States	Vertex Investigational Site	Spokane	Washington
United States	Vertex Investigational Site	Upland	California
United States	Vertex Investigational Site	Venice	Florida
United States	Vertex Investigational Site	Webster	Texas
United States	Vertex Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Estonia,  Lithuania,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	Long-term safety and tolerability of VX-509 treatment	Measured by clinical laboratory tests	Baseline through 104 weeks	No
Primary	Long-term safety and tolerability of VX-509 treatment	Measured by adverse events (AEs)	Baseline through 104 weeks	No
Primary	Long-term safety and tolerability of VX-509 treatment	Measured by electrocardiograms (ECGs)	Baseline through 104 weeks	No
Primary	Long-term safety and tolerability of VX-509 treatment	Measured by vital signs	Baseline through 104 weeks	No
Secondary	Proportion of subjects who achieve CDAI LDA (=10) or CDAI remission (=2.8)		Baseline through 104 weeks	No
Secondary	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	No
Secondary	Change from baseline in DAS28 using CRP (4-component) (DAS28 4[CRP])		Baseline through 104 weeks	No
Secondary	Proportion of subjects with DAS28 4(CRP) <2.6 (DAS remission)		Baseline through 104 weeks	No
Secondary	Proportion of subjects who achieve a moderate, good, or no response according to the EULAR response criteria from baseline		Baseline through 104 weeks	No
Secondary	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	No
Secondary	ACR hybrid scores		Baseline through 104 weeks	No
Secondary	Proportion of subjects who achieve ACR20/50/70 with erythrocyte sedimentation rate (ESR) and DAS28 4(ESR) response from baseline		Baseline through 104 weeks	No
Secondary	Proportion of subjects with DAS28 4(CRP) <3.2 (DAS LDA) from baseline		Baseline through 104 weeks	No
Secondary	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	No
Secondary	Change from baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI)		Baseline through 104 weeks	No
Secondary	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	No