Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated Identifier:
First received: April 27, 2012
Last updated: July 10, 2014
Last verified: July 2014

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 Intervention Phase
Rheumatoid Arthritis
Drug: VX-509
Drug: VX-509 matching placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measured by incidence of treatment-emergent adverse events

  • Safety and tolerability [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)

  • Safety and tolerability [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measured by 12-lead ECG outcomes

  • Safety and tolerability [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Measured by vital signs

Secondary Outcome Measures:
  • Proportion of subjects who achieve an ACR20-CRP response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses [ Time Frame: Week 12 and 24 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve remission as defined by DAS28-CRP response [ Time Frame: Week 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission [ Time Frame: Week 12 and 24 ] [ Designated as safety issue: No ]
  • Change from baseline in selected Patient Reported Outcomes (PROs) [ Time Frame: Week 12 and 24 ] [ Designated as safety issue: No ]
  • Change from baseline in DAS28- CRP [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 350
Study Start Date: April 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01590459

  Show 94 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Study Chair: Bradley Bloom, MD, FACR, FAAP Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated Identifier: NCT01590459     History of Changes
Other Study ID Numbers: VX11-509-102, 2011-004419-22
Study First Received: April 27, 2012
Last Updated: July 10, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Estonia: The State Agency of Medicine
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Slovakia: State Institute for Drug Control
Czech Republic: State Institute for Drug Control
Bulgaria: Bulgarian Drug Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Ukraine: Ministry of Health
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Romania: National Agency for Medicines and Medical Devices
Mexico: Federal Commission for Protection Against Health Risks

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases processed this record on March 03, 2015