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

April 30, 2015 updated by: Vertex Pharmaceuticals Incorporated

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Hillerød, Denmark
        • Vertex Investigational Site
      • Hjørring, Denmark
        • Vertex Investigational Site
  • Estonia
      • Tallinn, Estonia
        • Vertex Investigational Site
  • Lithuania
      • Vilnius, Lithuania
        • Vertex Investigational Site
  • Netherlands
      • Heerlen, Netherlands
        • Vertex Investigational Site
      • Utrecht, Netherlands
        • Vertex Investigational Site
  • South Africa
      • Johannesburg, South Africa
        • Vertex Investigational Site
      • Pretoria, South Africa
        • Vertex Investigational Site
      • Stellenbosch, South Africa
        • Vertex Investigational Site
  • United States
    • California
      • Stanford, California, United States
        • Vertex Investigational Site
      • Upland, California, United States
        • Vertex Investigational Site
    • Florida
      • Fort Lauderdale, Florida, United States
        • Vertex Investigational Site
      • Venice, Florida, United States
        • Vertex Investigational Site
      • West Palm Beach, Florida, United States
        • Vertex Investigational Site
    • Georgia
      • Canton, Georgia, United States
        • Vertex Investigational Site
      • Decatur, Georgia, United States
        • Vertex Investigational Site
    • Kansas
      • Kansas City, Kansas, United States
        • Vertex Investigational Site
    • Kentucky
      • Elizabethtown, Kentucky, United States
        • Vertex Investigational Site
    • Maryland
      • Frederick, Maryland, United States
        • Vertex Investigational Site
    • Nebraska
      • Lincoln, Nebraska, United States
        • Vertex Investigational Site
    • New York
      • Rochester, New York, United States
        • Vertex Investigational Site
    • North Carolina
      • Greenboro, North Carolina, United States
        • Vertex Investigational Site
    • Pennsylvania
      • Duncansville, Pennsylvania, United States
        • Vertex Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • Vertex Investigational Site
    • Tennessee
      • Memphis, Tennessee, United States
        • Vertex Investigational Site
    • Texas
      • Katy, Texas, United States
        • Vertex Investigational Site
      • San Antonio, Texas, United States
        • Vertex Investigational Site
      • Webster, Texas, United States
        • Vertex Investigational Site
    • Washington
      • Seattle, Washington, United States
        • Vertex Investigational Site
      • Spokane, Washington, United States
        • Vertex Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo Arm
Drug: VX-509 matching placebo
0 mg oral tablet
Experimental: VX-509 100 mg qd Arm
Drug: VX-509
50 mg oral tablet
Experimental: VX-509 200 mg qd Arm
Drug: VX-509
50 mg oral tablet
Experimental: VX-509 300 mg qd Arm
Drug: VX-509
50 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Week 12
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist
Time Frame: Week 12
Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
Time Frame: Week 12
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
Time Frame: Week 12
Week 12
ACR hybrid scores
Time Frame: Week 12
Week 12
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Time Frame: Week 12
Week 12
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
Time Frame: Week 6
Week 6
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
Week 12
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Time Frame: Week 12
Week 12
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Time Frame: Week 12
Week 12
Change from baseline in the Physical Component and Mental Health Components of the SF-36
Time Frame: Week 12
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vertex Pharmaceuticals Incorporated

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Bradley Bloom, MD, FACR, FAAP, Vertex Pharmaceuticals Incorporated

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VX12-509-103
  • 2012-003439-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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