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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01754935
• Other study ID #: VX12-509-103
• Secondary ID: 2012-003439-41
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2012
• Last updated: April 30, 2015
• Start date: January 2013
• Est. completion date: February 2014

Study information

• Verified date: April 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 HealthDenmark: Danish Health and Medicines AuthorityNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: February 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• VX-509
50 mg oral tablet
• VX-509 matching placebo
0 mg oral tablet

Locations

Country	Name	City	State
Denmark	Vertex Investigational Site	Hillerød
Denmark	Vertex Investigational Site	Hjørring
Estonia	Vertex Investigational Site	Tallinn
Lithuania	Vertex Investigational Site	Vilnius
Netherlands	Vertex Investigational Site	Heerlen
Netherlands	Vertex Investigational Site	Utrecht
South Africa	Vertex Investigational Site	Johannesburg
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	Frederick	Maryland
United States	Vertex Investigational Site	Greenboro	North Carolina
United States	Vertex Investigational Site	Kansas City	Kansas
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	Seattle	Washington
United States	Vertex Investigational Site	Spokane	Washington
United States	Vertex Investigational Site	Stanford	California
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,  Denmark,  Estonia,  Lithuania,  Netherlands,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		Week 12	No
Primary	Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])		Week 12	No
Primary	Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist		Week 12	No
Primary	Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist		Week 12	No
Primary	Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist		Week 12	No
Secondary	Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses		Week 12	No
Secondary	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		Week 12	No
Secondary	ACR hybrid scores		Week 12	No
Secondary	Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)		Week 12	No
Secondary	Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores		Week 6	No
Secondary	PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])		Week 12	No
Secondary	Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs		Week 12	No
Secondary	Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)		Week 12	No
Secondary	Change from baseline in the Physical Component and Mental Health Components of the SF-36		Week 12	No