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

NCT01754935 | Completed Phase 2

• 2 other identifiers: VX12-509-1032012-003439-41
• Study Type: interventional
• Target: 43
• Locations: 6 countries
• Sites: 30

Brief 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).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (5)

• 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

• Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])

  Week 12

• Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist

  Week 12

• Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist

  Week 12

• Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist

  Week 12

Secondary Outcomes (9)

• Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses

  Week 12

• 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

• ACR hybrid scores

  Week 12

• Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)

  Week 12

• Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores

  Week 6

Study Arms (4)

VX-509 100 mg qd Arm

EXPERIMENTAL

Drug: VX-509

VX-509 200 mg qd Arm

EXPERIMENTAL

Drug: VX-509

VX-509 300 mg qd Arm

EXPERIMENTAL

Drug: VX-509

Placebo Arm

PLACEBO COMPARATOR

Drug: VX-509 matching placebo

Interventions

VX-509 DRUG

50 mg oral tablet

VX-509 100 mg qd Arm; VX-509 200 mg qd Arm; VX-509 300 mg qd Arm

VX-509 matching placebo DRUG

0 mg oral tablet

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (30)

Vertex Investigational Site

Stanford, California, United States

Location

Vertex Investigational Site

Upland, California, United States

Location

Vertex Investigational Site

Fort Lauderdale, Florida, United States

Location

Vertex Investigational Site

Venice, Florida, United States

Location

Vertex Investigational Site

West Palm Beach, Florida, United States

Location

Vertex Investigational Site

Canton, Georgia, United States

Location

Vertex Investigational Site

Decatur, Georgia, United States

Location

Vertex Investigational Site

Kansas City, Kansas, United States

Location

Vertex Investigational Site

Elizabethtown, Kentucky, United States

Location

Vertex Investigational Site

Frederick, Maryland, United States

Location

Vertex Investigational Site

Lincoln, Nebraska, United States

Location

Vertex Investigational Site

Rochester, New York, United States

Location

Vertex Investigational Site

Greenboro, North Carolina, United States

Location

Vertex Investigational Site

Duncansville, Pennsylvania, United States

Location

Vertex Investigational Site

Charleston, South Carolina, United States

Location

Vertex Investigational Site

Memphis, Tennessee, United States

Location

Vertex Investigational Site

Katy, Texas, United States

Location

Vertex Investigational Site

San Antonio, Texas, United States

Location

Vertex Investigational Site

Webster, Texas, United States

Location

Vertex Investigational Site

Seattle, Washington, United States

Location

Vertex Investigational Site

Spokane, Washington, United States

Location

Vertex Investigational Site

Hillerød, Denmark

Location

Vertex Investigational Site

Hjørring, Denmark

Location

Vertex Investigational Site

Tallinn, Estonia

Location

Vertex Investigational Site

Vilnius, Lithuania

Location

Vertex Investigational Site

Heerlen, Netherlands

Location

Vertex Investigational Site

Utrecht, Netherlands

Location

Vertex Investigational Site

Johannesburg, South Africa

Location

Vertex Investigational Site

Pretoria, South Africa

Location

Vertex Investigational Site

Stellenbosch, South Africa

Location

Related Publications (1)

• Genovese MC, Yang F, Ostergaard M, Kinnman N. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings. Ann Rheum Dis. 2016 Nov;75(11):1979-1983. doi: 10.1136/annrheumdis-2015-208901. Epub 2016 Apr 15.

  PMID: 27084959 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

2-((2-(1H-pyrrolo(2,3-b)pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bradley Bloom, MD, FACR, FAAP

  Vertex Pharmaceuticals Incorporated

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 21, 2012
• Study Start: January 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: February 1, 2014
• Last Updated: May 19, 2015

Record last verified: 2015-04

Locations

ZA (3); NL (2); ES (1); US (21); DK (2); LI (1)