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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-509
VX-509 matching placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

VX-509 100 mg qd Arm

VX-509 200 mg qd Arm

VX-509 300 mg qd Arm

Placebo Arm

Arm Description

Outcomes

Primary Outcome Measures

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)
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist

Secondary Outcome Measures

Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
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
ACR hybrid scores
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Change from baseline in the Physical Component and Mental Health Components of the SF-36

Full Information

First Posted
December 18, 2012
Last Updated
April 30, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT01754935
Brief Title
A Magnetic Resonance Imaging Study and Arthroscopic Biopsy Substudy in Subjects With Active Rheumatoid Arthritis Receiving VX-509, an Oral JAK3 Inhibitor
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).
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, and a broad range of other autoimmune diseases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VX-509 100 mg qd Arm
Arm Type
Experimental
Arm Title
VX-509 200 mg qd Arm
Arm Type
Experimental
Arm Title
VX-509 300 mg qd Arm
Arm Type
Experimental
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
VX-509
Intervention Description
50 mg oral tablet
Intervention Type
Drug
Intervention Name(s)
VX-509 matching placebo
Intervention Description
0 mg oral tablet
Primary Outcome Measure Information:
Title
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)
Time Frame
Week 12
Title
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Time Frame
Week 12
Title
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Time Frame
Week 12
Title
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Time Frame
Week 12
Title
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
Time Frame
Week 12
Title
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
Time Frame
Week 12
Title
ACR hybrid scores
Time Frame
Week 12
Title
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Time Frame
Week 12
Title
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
Time Frame
Week 6
Title
PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])
Time Frame
Week 12
Title
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Time Frame
Week 12
Title
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Time Frame
Week 12
Title
Change from baseline in the Physical Component and Mental Health Components of the SF-36
Time Frame
Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bradley Bloom, MD, FACR, FAAP
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Chair
Facility Information:
Facility Name
Vertex Investigational Site
City
Stanford
State/Province
California
Country
United States
Facility Name
Vertex Investigational Site
City
Upland
State/Province
California
Country
United States
Facility Name
Vertex Investigational Site
City
Fort Lauderdale
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Venice
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
West Palm Beach
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Canton
State/Province
Georgia
Country
United States
Facility Name
Vertex Investigational Site
City
Decatur
State/Province
Georgia
Country
United States
Facility Name
Vertex Investigational Site
City
Kansas City
State/Province
Kansas
Country
United States
Facility Name
Vertex Investigational Site
City
Elizabethtown
State/Province
Kentucky
Country
United States
Facility Name
Vertex Investigational Site
City
Frederick
State/Province
Maryland
Country
United States
Facility Name
Vertex Investigational Site
City
Lincoln
State/Province
Nebraska
Country
United States
Facility Name
Vertex Investigational Site
City
Rochester
State/Province
New York
Country
United States
Facility Name
Vertex Investigational Site
City
Greenboro
State/Province
North Carolina
Country
United States
Facility Name
Vertex Investigational Site
City
Duncansville
State/Province
Pennsylvania
Country
United States
Facility Name
Vertex Investigational Site
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
Vertex Investigational Site
City
Memphis
State/Province
Tennessee
Country
United States
Facility Name
Vertex Investigational Site
City
Katy
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
Webster
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Vertex Investigational Site
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Vertex Investigational Site
City
Hillerød
Country
Denmark
Facility Name
Vertex Investigational Site
City
Hjørring
Country
Denmark
Facility Name
Vertex Investigational Site
City
Tallinn
Country
Estonia
Facility Name
Vertex Investigational Site
City
Vilnius
Country
Lithuania
Facility Name
Vertex Investigational Site
City
Heerlen
Country
Netherlands
Facility Name
Vertex Investigational Site
City
Utrecht
Country
Netherlands
Facility Name
Vertex Investigational Site
City
Johannesburg
Country
South Africa
Facility Name
Vertex Investigational Site
City
Pretoria
Country
South Africa
Facility Name
Vertex Investigational Site
City
Stellenbosch
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
27084959
Citation
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.
Results Reference
derived

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

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