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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01590459
Recruitment Status : Completed
First Posted : May 3, 2012
Last Update Posted : November 20, 2015
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: VX-509 Drug: VX-509 matching placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 359 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : April 2012
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. 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 ]
  2. Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP) [ Time Frame: Week 12 ]
  3. Safety and tolerability [ Time Frame: Week 12 ]
    Measured by incidence of treatment-emergent adverse events

  4. Safety and tolerability [ Time Frame: Week 12 ]
    Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)

  5. Safety and tolerability [ Time Frame: Week 12 ]
    Measured by 12-lead ECG outcomes

  6. Safety and tolerability [ Time Frame: Week 12 ]
    Measured by vital signs

Secondary Outcome Measures :
  1. Proportion of subjects who achieve an ACR20-CRP response [ Time Frame: Week 24 ]
  2. Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses [ Time Frame: Week 12 and 24 ]
  3. 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 ]
  4. Proportion of subjects who achieve remission as defined by DAS28-CRP response [ Time Frame: Week 12 and 24 ]
  5. Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission [ Time Frame: Week 12 and 24 ]
  6. Change from baseline in selected Patient Reported Outcomes (PROs) [ Time Frame: Week 12 and 24 ]
  7. Change from baseline in DAS28- CRP [ Time Frame: Week 24 ]
  8. Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs [ Time Frame: Week 24 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01590459

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Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
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Study Chair: Ali Ashrafzadeh, MD, FACR Quintiles, Inc.

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Responsible Party: Vertex Pharmaceuticals Incorporated Identifier: NCT01590459     History of Changes
Other Study ID Numbers: VX11-509-102
2011-004419-22 ( EudraCT Number )
First Posted: May 3, 2012    Key Record Dates
Last Update Posted: November 20, 2015
Last Verified: October 2015
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors