Clinical trial NCT01052194: A 12-week Study of 4 Doses of VX-509 in Subjects With Active Rheumatoid Arthritis
Official title: A 12-week, Double-blind, Randomized, Parallel-group, Placebo-controlled Study of 4 Doses of VX-509 in Subjects With Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2010-01-20
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
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 safety and assess initial efficacy of VX-509, a JAK3 inhibitor, for treatment of subjects with active RA. This study will assess the clinical response of 4 doses of VX-509 compared to placebo when administered for 12 weeks to patients with active RA. The study will also evaluate the safety and tolerability of VX-509 compared to placebo when administered for 12 weeks to subjects with active RA.


Eligibility criteria: Inclusion Criteria:

* All subjects must have been diagnosed with RA as defined by the ACR revised criteria with disease duration of at least 6 months from confirmed diagnosis
* Subjects must have a swollen joint count of ≥6 out of 28 joints and tender joint count of ≥6 out of 28 joints. Joints that have had prior surgery are to be excluded from the joint count.
* Baseline CRP level must be 1.5 times greater than the upper limit of normal at Screening.
* Subjects must have failed at least 1 nonbiologic DMARD for any reason.
* Subjects may have previously failed no more than 1 biologic DMARD and discontinued treatment for reasons other than inadequate response. Subjects must not have been treated with Rituximab previously.
* Subjects must be willing to comply with contraception requirements.

Exclusion Criteria:

* Subjects with inflammatory rheumatological disorders other than RA.
* History or evidence of a clinically significant disorder other than RA (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric disorders), condition or disease 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 clinically important abnormalities in screening physical examination or in screening laboratory test results (including the presence of either hepatitis B surface antigen, hepatitis C virus antibody, or HIV types 1 -- Subjects with elevation in alanine aminotransferase or aspartate aminotransferase above the upper limit of normal.
* History of hematologic disorders including neutropenia and thrombocytopenia.
* Subjects with an acute or chronic active infection requiring systemic antimicrobial treatment, or subjects who are at high risk of developing an infection due to a compromised immune system. Antifungals for onychomycosis or low-dose antibiotics for rosacea, that are not inhibitors or inducers of CYP3A, will be allowed.
* Subjects who require concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A.
* Subjects who have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1.
* Subjects who have planned major surgery (e.g., joint replacement) or any procedures during the study.
* Have received any live, attenuated vaccinations within 1 month prior to study drug administration.
* History of drug or alcohol abuse or excessive alcohol as determined by the investigator, during the last 12 months before the screening visit.
* History of 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 an ACR20 response
timeFrame: Week 12
measure: Change from baseline in DAS28
timeFrame: Week 12
Secondary outcomes:
measure: Proportion of subjects who achieve an ACR50,70 response
timeFrame: Week 12
measure: Proportion of subjects who achieve moderate or good EULAR response
timeFrame: Week 12
measure: Magnitude of improvement in the components of the ACR response criteria
timeFrame: Week 12
measure: Pharmacokinetics of VX-509
timeFrame: Week 6
measure: Pharmacodynamics (PD) of biomarker responses
timeFrame: Week 6
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: La Mesa
country: United States
state: California
city: Trumbull
country: United States
state: Connecticut
city: Tampa
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Venice
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Worcester
country: United States
state: Massachusetts
city: St. Louis
country: United States
state: Missouri
city: Charlotte
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Duncansville
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Spokane
country: United States
state: Washington
city: Clarksburg
country: United States
state: West Virginia
city: Antwerpen
country: Belgium
city: Karlovac
country: Croatia
city: Opatija
country: Croatia
city: Zagreb
country: Croatia
city: Erfurt
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hildesheim
country: Germany
city: Nauheim
country: Germany
city: Zerbst
country: Germany
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Veszprem
country: Hungary
city: Elblag
country: Poland
city: Limanow
country: Poland
city: Lublin
country: Poland
city: Wroclaw
country: Poland
city: San Juan
country: Puerto Rico
city: Baia Mare
country: Romania
city: Braila
country: Romania
city: Bucharest
country: Romania
city: Galati
country: Romania
city: Kemerovo
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Vladimir
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Belgrade
country: Serbia
city: Niska Banja
country: Serbia
Study officials:
affiliation: Vertex Pharmaceuticals Incorporated
name: Medical Monitor
role: STUDY_DIRECTOR
References: