24-week Study With Open Label Extension of VX-509, an Oral JAK3 Inhibitor, in Subjects Taking Methotrexate

October 23, 2015 updated by: Vertex Pharmaceuticals Incorporated

A 24-week, Double-Blind, Randomized, Parallel Group, Placebo-Controlled, Phase 2 Study of Different Doses of VX-509 in Adult Subjects With Active Rheumatoid Arthritis on Stable Methotrexate Therapy With 104-Week Open Label Extension

This study is designed to evaluate the safety and efficacy of VX-509, an oral JAK3 inhibitor, for treatment of subjects with active RA who have had an inadequate response to Methotrexate.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

359

Phase

  • 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

  • Argentina
      • Buenos Aires, Argentina, C1121ABE
        • Vertex Investigational Site
      • Buenos Aires, Argentina, C1425EKG
        • Vertex Investigational Site
      • Buenos Aires, Argentina, C1426AAL
        • Vertex Investigational Site
      • Santa Fe, Argentina
        • Vertex Investigational Site
  • Bulgaria
      • Plovdiv, Bulgaria, 4002
        • Vertex Investigational Site
      • Sevlievo, Bulgaria
        • Vertex Investigational Site
      • Sofia, Bulgaria, 1233
        • Vertex Investigational Site
      • Sofia, Bulgaria, 1784
        • Vertex Investigational Site
      • Veliko Tarnovo, Bulgaria, 5000
        • Vertex Investigational Site
  • Czech Republic
      • Brno, Czech Republic, 638 00
        • Vertex Investigational Site
      • Bruntal, Czech Republic, 792 01
        • Vertex Investigational Site
      • Mlada Boleslav, Czech Republic
        • Vertex Investigational Site
      • Ostrava - Trebovice, Czech Republic
        • Vertex Investigational Site
      • Praha 2, Czech Republic, 760 01
        • Vertex Investigational Site
      • Zlin, Czech Republic, 760 01
        • Vertex Investigational Site
  • Estonia
      • Tallinn, Estonia, 10117
        • Vertex Investigational Site
      • Tallinn, Estonia, 10128
        • Vertex Investigational Site
      • Tallinn, Estonia, 11312
        • Vertex Investigational Site
      • Tallinn, Estonia, 13419
        • Vertex Investigational Site
  • Germany
      • Koeln, Germany, 50924
        • Vertex Investigational Site
      • Leipzig, Germany, 4103
        • Vertex Investigational Site
      • Wuerzburg, Germany, 97080
        • Vertex Investigational Site
      • Zerbst, Germany, 39261
        • Vertex Investigational Site
  • Hungary
      • Baja, Hungary, 6500
        • Vertex Investigational Site
      • Budapest, Hungary, 1023
        • Vertex Investigational Site
      • Budapest, Hungary, 1036
        • Vertex Investigational Site
      • Szikszó, Hungary, 3800
        • Vertex Investigational Site
  • Mexico
      • Chihuahua, Mexico
        • Vertex Investigational Site
      • Cuauhtemoc, Mexico
        • Vertex Investigational Site
      • San Luis Potos, Mexico
        • Vertex Investigational Site
      • San Miguel Chapultepec, Mexico
        • Vertex Investigational Site
  • Poland
      • Bialystok, Poland, 15-879
        • Vertex Investigational Site
      • Elblag, Poland, 82-300
        • Vertex Investigational Site
      • Krakow, Poland, 30-510
        • Vertex Investigational Site
      • Lublin, Poland, 20-607
        • Vertex Investigational Site
      • Poznan, Poland, 60-218
        • Vertex Investigational Site
      • Poznan, Poland, 60-539
        • Vertex Investigational Site
      • Torun, Poland, 87-100
        • Vertex Investigational Site
      • Warszawa, Poland, 00-029
        • Vertex Investigational Site
      • Warszawa, Poland, 02-118
        • Vertex Investigational Site
      • Warszawa, Poland, 04-141
        • Vertex Investigational Site
  • Romania
      • Braila, Romania
        • Vertex Investigational Site
      • Bucuresti, Romania, 010976
        • Vertex Investigational Site
      • Bucuresti, Romania, 011198
        • Vertex Investigational Site
      • Judetul Galati, Romania
        • Vertex Investigational Site
  • Russian Federation
      • Kemerovo, Russian Federation
        • Vertex Investigational Site
      • Moscow, Russian Federation
        • Vertex Investigational Site
      • Ryazan, Russian Federation
        • Vertex Investigational Site
      • St. Petersburg, Russian Federation, 190068
        • Vertex Investigational Site
      • St. Petersburg, Russian Federation, 191186
        • Vertex Investigational Site
      • Yaroslavl, Russian Federation
        • Vertex Investigational Site
  • Serbia
      • Belgrade, Serbia, 11000
        • Vertex Investigational Site
      • Niska Banja, Serbia, 18205
        • Vertex Investigational Site
      • Novi Sad, Serbia, 21000
        • Vertex Investigational Site
  • Slovakia
      • Bratislava, Slovakia, 84104
        • Vertex Investigational Site
      • Dunajska Streda, Slovakia
        • Vertex Investigational Site
      • Poprad, Slovakia, 5801
        • Vertex Investigational Site
      • Rimavska Sobota, Slovakia, 97901
        • Vertex Investigational Site
  • Ukraine
      • Donetsk, Ukraine
        • Vertex Investigational Site
      • Kharkiv, Ukraine
        • Vertex Investigational Site
      • Lviv, Ukraine
        • Vertex Investigational Site
      • Odesa, Ukraine
        • Vertex Investigational Site
      • Vinnytsia, Ukraine
        • Vertex Investigational Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States
        • Vertex Investigational Site
      • Huntsville, Alabama, United States
        • Vertex Investigational Site
    • California
      • Long Beach, California, United States
        • Vertex Investigational Site
      • Tustin, California, United States
        • Vertex Investigational Site
    • Florida
      • Boca Raton, Florida, United States
        • Vertex Investigational Site
      • Daytona Beach, Florida, United States
        • Vertex Investigational Site
      • New Port Richey, Florida, United States
        • Vertex Investigational Site
      • North Miami Beach, Florida, United States
        • Vertex Investigational Site
      • Ocala, Florida, United States
        • Vertex Investigational Site
      • Tampa, Florida, United States
        • Vertex Investigational Site
    • Illinois
      • Springfield, Illinois, United States
        • Vertex Investigational Site
    • Kansas
      • Wichita, Kansas, United States
        • Vertex Investigational Site
    • Michigan
      • Kalamazoo, Michigan, United States
        • Vertex Investigational Site
    • Missouri
      • St. Louis, Missouri, United States
        • Vertex Investigational Site
    • Nebraska
      • Omaha, Nebraska, United States
        • Vertex Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States
        • Vertex Investigational Site
    • New Jersey
      • Clifton, New Jersey, United States
        • Vertex Investigational Site
      • Freehold, New Jersey, United States
        • Vertex Investigational Site
    • New York
      • Brooklyn, New York, United States
        • Vertex Investigational Site
    • North Carolina
      • Charlotte, North Carolina, United States
        • Vertex Investigational Site
      • Durham, North Carolina, United States
        • Vertex Investigational Site
      • Hickory, North Carolina, United States
        • Vertex Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • Vertex Investigational Site
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States
        • Vertex Investigational Site
      • Duncansville, Pennsylvania, United States
        • Vertex Investigational Site
    • Tennessee
      • Jackson, Tennessee, United States
        • Vertex Investigational Site
    • Texas
      • Austin, Texas, United States
        • Vertex Investigational Site
      • Houston, Texas, United States
        • Vertex Investigational Site
      • Mesquite, Texas, United States
        • Vertex Investigational Site
      • San Antonio, Texas, United States
        • Vertex Investigational Site
    • West Virginia
      • Clarksburg, West Virginia, 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

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female subjects, between 18 and 80 years of age (inclusive)
  • All subjects must have been diagnosed with RA
  • Must have a swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
  • Baseline CRP level must be above the upper limit of normal
  • All subjects must have been receiving stable MTX coadministered with folic or folinic acid (at least 5 mg/week)
  • Subjects may remain on 1 nonsteroidal anti-inflammatory medication during the study (aspirin ≤ 325 mg/day is allowed).
  • Subjects must not have received prior treatment with a JAK inhibitor
  • Subjects who are on an additional nonbiologic DMARD (e.g., sulfasalazine) must be willing to discontinue that DMARD after signing consent, except for hydroxychloroquine
  • Subjects may have received previous therapy with a single TNF inhibitor (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol)
  • Females must have a negative pregnancy test prior to study dosing
  • Sexually active subjects and their partners must agree to contraceptive requirements

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.
  • Subjects with inflammatory, rheumatological disorders other than RA
  • Pregnant or nursing female subjects
  • Subjects who have a female partner who is pregnant, nursing, or planning to become pregnant
  • Subjects who have planned major surgery (e.g., joint replacement) or procedures during the study
  • History of drug abuse or positive drug screen
  • History of alcohol 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.

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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-509 150 mg qd Arm
Drug: VX-509
50 mg oral tablet
EXPERIMENTAL: VX-509 100 mg bid Arm
Drug: VX-509
50 mg oral tablet
EXPERIMENTAL: VX-509 200 mg qd Arm
Drug: VX-509
50 mg oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of subjects who achieve a 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP) response
Time Frame: Week 12
Week 12
Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)
Time Frame: Week 12
Week 12
Safety and tolerability
Time Frame: Week 12
Measured by incidence of treatment-emergent adverse events
Week 12
Safety and tolerability
Time Frame: Week 12
Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)
Week 12
Safety and tolerability
Time Frame: Week 12
Measured by 12-lead ECG outcomes
Week 12
Safety and tolerability
Time Frame: Week 12
Measured by vital signs
Week 12

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of subjects who achieve an ACR20-CRP response
Time Frame: Week 24
Week 24
Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses
Time Frame: Week 12 and 24
Week 12 and 24
Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria
Time Frame: Week 12 and 24
Week 12 and 24
Proportion of subjects who achieve remission as defined by DAS28-CRP response
Time Frame: Week 12 and 24
Week 12 and 24
Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission
Time Frame: Week 12 and 24
Week 12 and 24
Change from baseline in selected Patient Reported Outcomes (PROs)
Time Frame: Week 12 and 24
Week 12 and 24
Change from baseline in DAS28- CRP
Time Frame: Week 24
Week 24
Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs
Time Frame: Week 24
Week 24

Collaborators and Investigators

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

Sponsor

Vertex Pharmaceuticals Incorporated

Investigators

  • Study Chair: Ali Ashrafzadeh, MD, FACR, Quintiles, Inc.

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

April 1, 2012

Primary Completion (ACTUAL)

July 1, 2014

Study Completion (ACTUAL)

July 1, 2014

Study Registration Dates

First Submitted

April 27, 2012

First Submitted That Met QC Criteria

May 1, 2012

First Posted (ESTIMATE)

May 3, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

November 20, 2015

Last Update Submitted That Met QC Criteria

October 23, 2015

Last Verified

October 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VX11-509-102
  • 2011-004419-22 (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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