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

NCT01590459 | Completed Phase 2 DMC

• 2 other identifiers: VX11-509-1022011-004419-22
• Study Type: interventional
• Target: 359
• Locations: 14 countries
• Sites: 94

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (6)

• 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

  Week 12

• Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)

  Week 12

• Safety and tolerability

  Measured by incidence of treatment-emergent adverse events

  Week 12

• Safety and tolerability

  Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)

  Week 12

• Safety and tolerability

  Measured by 12-lead ECG outcomes

  Week 12

• Safety and tolerability

  Measured by vital signs

  Week 12

Secondary Outcomes (8)

• Proportion of subjects who achieve an ACR20-CRP response

  Week 24

• Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses

  Week 12 and 24

• Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria

  Week 12 and 24

• Proportion of subjects who achieve remission as defined by DAS28-CRP response

  Week 12 and 24

• Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission

  Week 12 and 24

Study Arms (5)

Placebo Arm

PLACEBO COMPARATOR

Drug: VX-509 matching placebo

VX-509 100 mg qd Arm

EXPERIMENTAL

Drug: VX-509

VX-509 150 mg qd Arm

EXPERIMENTAL

Drug: VX-509

VX-509 100 mg bid Arm

EXPERIMENTAL

Drug: VX-509

VX-509 200 mg qd Arm

EXPERIMENTAL

Drug: VX-509

Interventions

VX-509 DRUG

50 mg oral tablet

VX-509 100 mg bid Arm; VX-509 100 mg qd Arm; VX-509 150 mg qd Arm; VX-509 200 mg qd Arm

VX-509 matching placebo DRUG

0 mg oral tablet

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (94)

Vertex Investigational Site

Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Long Beach, California, United States

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Tustin, California, United States

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Boca Raton, Florida, United States

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Daytona Beach, Florida, United States

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New Port Richey, Florida, United States

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North Miami Beach, Florida, United States

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Ocala, Florida, United States

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Tampa, Florida, United States

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Springfield, Illinois, United States

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Wichita, Kansas, United States

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Kalamazoo, Michigan, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Clifton, New Jersey, United States

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Freehold, New Jersey, United States

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Brooklyn, New York, United States

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Charlotte, North Carolina, United States

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Durham, North Carolina, United States

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Hickory, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Bethlehem, Pennsylvania, United States

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Duncansville, Pennsylvania, United States

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Jackson, Tennessee, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Mesquite, Texas, United States

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San Antonio, Texas, United States

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Clarksburg, West Virginia, United States

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Buenos Aires, C1121ABE, Argentina

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Buenos Aires, C1425EKG, Argentina

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Buenos Aires, C1426AAL, Argentina

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Santa Fe, Argentina

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Plovdiv, 4002, Bulgaria

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Sevlievo, Bulgaria

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Sofia, 1233, Bulgaria

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Sofia, 1784, Bulgaria

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Veliko Tarnovo, 5000, Bulgaria

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Brno, 638 00, Czechia

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Bruntál, 792 01, Czechia

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Mladá Boleslav, Czechia

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Ostrava - Trebovice, Czechia

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Prague, 760 01, Czechia

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Zlín, 760 01, Czechia

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Tallinn, 10117, Estonia

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Tallinn, 10128, Estonia

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Tallinn, 11312, Estonia

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Tallinn, 13419, Estonia

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Cologne, 50924, Germany

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Leipzig, 4103, Germany

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Würzburg, 97080, Germany

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Zerbst, 39261, Germany

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Baja, 6500, Hungary

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Budapest, 1023, Hungary

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Budapest, 1036, Hungary

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Szikszó, 3800, Hungary

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Chihuahua City, Mexico

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Cuauhtémoc, Mexico

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San Luis Potos, Mexico

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San Miguel Chapultepec, Mexico

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Bialystok, 15-879, Poland

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Elblag, 82-300, Poland

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Krakow, 30-510, Poland

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Lublin, 20-607, Poland

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Poznan, 60-218, Poland

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Poznan, 60-539, Poland

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Torun, 87-100, Poland

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Warsaw, 00-029, Poland

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Warsaw, 02-118, Poland

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Warsaw, 04-141, Poland

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Brăila, Romania

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Bucharest, 010976, Romania

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Bucharest, 011198, Romania

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Judetul Galati, Romania

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Kemerovo, Russia

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Moscow, Russia

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Ryazan, Russia

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Saint Petersburg, 190068, Russia

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Saint Petersburg, 191186, Russia

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Yaroslavl, Russia

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Belgrade, 11000, Serbia

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Niška Banja, 18205, Serbia

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Novi Sad, 21000, Serbia

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Bratislava, 84104, Slovakia

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Dunajská Streda, Slovakia

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Poprad, 5801, Slovakia

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Rimavská Sobota, 97901, Slovakia

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Donetsk, Ukraine

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Kharkiv, Ukraine

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Lviv, Ukraine

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Odesa, Ukraine

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Vinnytsia, Ukraine

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MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

2-((2-(1H-pyrrolo(2,3-b)pyridin-3-yl)pyrimidin-4-yl)amino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ali Ashrafzadeh, MD, FACR

  Quintiles, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2012
• First Posted: May 3, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: November 20, 2015

Record last verified: 2015-10

Locations

HU (4); RO (4); SE (3); SL (4); ES (4); RU (6); CZ (6); DE (4); US (31); ME (4); AR (4); UA (5); PL (10); BU (5)