Clinical trial NCT01590459: 24-week Study With Open Label Extension of VX-509, an Oral JAK3 Inhibitor, in Subjects Taking Methotrexate
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2012-05-03
Enrollment: 359
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Week 12
measure: Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)
timeFrame: Week 12
measure: Safety and tolerability
timeFrame: Week 12
measure: Safety and tolerability
timeFrame: Week 12
measure: Safety and tolerability
timeFrame: Week 12
measure: Safety and tolerability
timeFrame: Week 12
Secondary outcomes:
measure: Proportion of subjects who achieve an ACR20-CRP response
timeFrame: Week 24
measure: Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses
timeFrame: Week 12 and 24
measure: Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria
timeFrame: Week 12 and 24
measure: Proportion of subjects who achieve remission as defined by DAS28-CRP response
timeFrame: Week 12 and 24
measure: Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission
timeFrame: Week 12 and 24
measure: Change from baseline in selected Patient Reported Outcomes (PROs)
timeFrame: Week 12 and 24
measure: Change from baseline in DAS28- CRP
timeFrame: Week 24
measure: Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs
timeFrame: Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Vertex Investigational Site
state: Alabama
city: Huntsville
country: United States
facility: Vertex Investigational Site
state: Alabama
city: Long Beach
country: United States
facility: Vertex Investigational Site
state: California
city: Tustin
country: United States
facility: Vertex Investigational Site
state: California
city: Boca Raton
country: United States
facility: Vertex Investigational Site
state: Florida
city: Daytona Beach
country: United States
facility: Vertex Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Vertex Investigational Site
state: Florida
city: North Miami Beach
country: United States
facility: Vertex Investigational Site
state: Florida
city: Ocala
country: United States
facility: Vertex Investigational Site
state: Florida
city: Tampa
country: United States
facility: Vertex Investigational Site
state: Florida
city: Springfield
country: United States
facility: Vertex Investigational Site
state: Illinois
city: Wichita
country: United States
facility: Vertex Investigational Site
state: Kansas
city: Kalamazoo
country: United States
facility: Vertex Investigational Site
state: Michigan
city: St. Louis
country: United States
facility: Vertex Investigational Site
state: Missouri
city: Omaha
country: United States
facility: Vertex Investigational Site
state: Nebraska
city: Las Vegas
country: United States
facility: Vertex Investigational Site
state: Nevada
city: Clifton
country: United States
facility: Vertex Investigational Site
state: New Jersey
city: Freehold
country: United States
facility: Vertex Investigational Site
state: New Jersey
city: Brooklyn
country: United States
facility: Vertex Investigational Site
state: New York
city: Charlotte
country: United States
facility: Vertex Investigational Site
state: North Carolina
city: Durham
country: United States
facility: Vertex Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Vertex Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Vertex Investigational Site
state: Oklahoma
city: Bethlehem
country: United States
facility: Vertex Investigational Site
state: Pennsylvania
city: Duncansville
country: United States
facility: Vertex Investigational Site
state: Pennsylvania
city: Jackson
country: United States
facility: Vertex Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Vertex Investigational Site
state: Texas
city: Houston
country: United States
facility: Vertex Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Vertex Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Vertex Investigational Site
state: Texas
city: Clarksburg
country: United States
facility: Vertex Investigational Site
state: West Virginia
city: Buenos Aires
country: Argentina
facility: Vertex Investigational Site
city: Buenos Aires
country: Argentina
facility: Vertex Investigational Site
city: Buenos Aires
country: Argentina
facility: Vertex Investigational Site
city: Santa Fe
country: Argentina
facility: Vertex Investigational Site
city: Plovdiv
country: Bulgaria
facility: Vertex Investigational Site
city: Sevlievo
country: Bulgaria
facility: Vertex Investigational Site
city: Sofia
country: Bulgaria
facility: Vertex Investigational Site
city: Sofia
country: Bulgaria
facility: Vertex Investigational Site
city: Veliko Tarnovo
country: Bulgaria
facility: Vertex Investigational Site
city: Brno
country: Czech Republic
facility: Vertex Investigational Site
city: Bruntal
country: Czech Republic
facility: Vertex Investigational Site
city: Mlada Boleslav
country: Czech Republic
facility: Vertex Investigational Site
city: Ostrava - Trebovice
country: Czech Republic
facility: Vertex Investigational Site
city: Praha 2
country: Czech Republic
facility: Vertex Investigational Site
city: Zlin
country: Czech Republic
facility: Vertex Investigational Site
city: Tallinn
country: Estonia
facility: Vertex Investigational Site
city: Tallinn
country: Estonia
facility: Vertex Investigational Site
city: Tallinn
country: Estonia
facility: Vertex Investigational Site
city: Tallinn
country: Estonia
facility: Vertex Investigational Site
city: Koeln
country: Germany
facility: Vertex Investigational Site
city: Leipzig
country: Germany
facility: Vertex Investigational Site
city: Wuerzburg
country: Germany
facility: Vertex Investigational Site
city: Zerbst
country: Germany
facility: Vertex Investigational Site
city: Baja
country: Hungary
facility: Vertex Investigational Site
city: Budapest
country: Hungary
facility: Vertex Investigational Site
city: Budapest
country: Hungary
facility: Vertex Investigational Site
city: Szikszó
country: Hungary
facility: Vertex Investigational Site
city: Chihuahua
country: Mexico
facility: Vertex Investigational Site
city: Cuauhtemoc
country: Mexico
facility: Vertex Investigational Site
city: San Luis Potos
country: Mexico
facility: Vertex Investigational Site
city: San Miguel Chapultepec
country: Mexico
facility: Vertex Investigational Site
city: Bialystok
country: Poland
facility: Vertex Investigational Site
city: Elblag
country: Poland
facility: Vertex Investigational Site
city: Krakow
country: Poland
facility: Vertex Investigational Site
city: Lublin
country: Poland
facility: Vertex Investigational Site
city: Poznan
country: Poland
facility: Vertex Investigational Site
city: Poznan
country: Poland
facility: Vertex Investigational Site
city: Torun
country: Poland
facility: Vertex Investigational Site
city: Warszawa
country: Poland
facility: Vertex Investigational Site
city: Warszawa
country: Poland
facility: Vertex Investigational Site
city: Warszawa
country: Poland
facility: Vertex Investigational Site
city: Braila
country: Romania
facility: Vertex Investigational Site
city: Bucuresti
country: Romania
facility: Vertex Investigational Site
city: Bucuresti
country: Romania
facility: Vertex Investigational Site
city: Judetul Galati
country: Romania
facility: Vertex Investigational Site
city: Kemerovo
country: Russian Federation
facility: Vertex Investigational Site
city: Moscow
country: Russian Federation
facility: Vertex Investigational Site
city: Ryazan
country: Russian Federation
facility: Vertex Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Vertex Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Vertex Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Vertex Investigational Site
city: Belgrade
country: Serbia
facility: Vertex Investigational Site
city: Niska Banja
country: Serbia
facility: Vertex Investigational Site
city: Novi Sad
country: Serbia
facility: Vertex Investigational Site
city: Bratislava
country: Slovakia
facility: Vertex Investigational Site
city: Dunajska Streda
country: Slovakia
facility: Vertex Investigational Site
city: Poprad
country: Slovakia
facility: Vertex Investigational Site
city: Rimavska Sobota
country: Slovakia
facility: Vertex Investigational Site
city: Donetsk
country: Ukraine
facility: Vertex Investigational Site
city: Kharkiv
country: Ukraine
facility: Vertex Investigational Site
city: Lviv
country: Ukraine
facility: Vertex Investigational Site
city: Odesa
country: Ukraine
facility: Vertex Investigational Site
city: Vinnytsia
country: Ukraine
facility: Vertex Investigational Site
Study officials:
affiliation: Quintiles, Inc.
name: Ali Ashrafzadeh, MD, FACR
role: STUDY_CHAIR
References: