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

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
VX-509
VX-509 matching placebo
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
  • Vertex Investigational Site
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo Arm

VX-509 100 mg qd Arm

VX-509 150 mg qd Arm

VX-509 100 mg bid Arm

VX-509 200 mg qd Arm

Arm Description

Outcomes

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
Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)
Safety and tolerability
Measured by incidence of treatment-emergent adverse events
Safety and tolerability
Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)
Safety and tolerability
Measured by 12-lead ECG outcomes
Safety and tolerability
Measured by vital signs

Secondary Outcome Measures

Proportion of subjects who achieve an ACR20-CRP response
Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses
Proportion of subjects who achieve a moderate or good response according to the European League Against Rheumatism (EULAR) response criteria
Proportion of subjects who achieve remission as defined by DAS28-CRP response
Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission
Change from baseline in selected Patient Reported Outcomes (PROs)
Change from baseline in DAS28- CRP
Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs

Full Information

First Posted
April 27, 2012
Last Updated
October 23, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT01590459
Brief Title
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

2. Study Status

Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
359 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Title
VX-509 100 mg qd Arm
Arm Type
Experimental
Arm Title
VX-509 150 mg qd Arm
Arm Type
Experimental
Arm Title
VX-509 100 mg bid Arm
Arm Type
Experimental
Arm Title
VX-509 200 mg qd Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
VX-509
Intervention Description
50 mg oral tablet
Intervention Type
Drug
Intervention Name(s)
VX-509 matching placebo
Intervention Description
0 mg oral tablet
Primary Outcome Measure Information:
Title
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
Title
Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP)
Time Frame
Week 12
Title
Safety and tolerability
Description
Measured by incidence of treatment-emergent adverse events
Time Frame
Week 12
Title
Safety and tolerability
Description
Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)
Time Frame
Week 12
Title
Safety and tolerability
Description
Measured by 12-lead ECG outcomes
Time Frame
Week 12
Title
Safety and tolerability
Description
Measured by vital signs
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Proportion of subjects who achieve an ACR20-CRP response
Time Frame
Week 24
Title
Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses
Time Frame
Week 12 and 24
Title
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
Title
Proportion of subjects who achieve remission as defined by DAS28-CRP response
Time Frame
Week 12 and 24
Title
Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission
Time Frame
Week 12 and 24
Title
Change from baseline in selected Patient Reported Outcomes (PROs)
Time Frame
Week 12 and 24
Title
Change from baseline in DAS28- CRP
Time Frame
Week 24
Title
Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs
Time Frame
Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ali Ashrafzadeh, MD, FACR
Organizational Affiliation
Quintiles, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Vertex Investigational Site
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Vertex Investigational Site
City
Huntsville
State/Province
Alabama
Country
United States
Facility Name
Vertex Investigational Site
City
Long Beach
State/Province
California
Country
United States
Facility Name
Vertex Investigational Site
City
Tustin
State/Province
California
Country
United States
Facility Name
Vertex Investigational Site
City
Boca Raton
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Daytona Beach
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
New Port Richey
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
North Miami Beach
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Ocala
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Vertex Investigational Site
City
Springfield
State/Province
Illinois
Country
United States
Facility Name
Vertex Investigational Site
City
Wichita
State/Province
Kansas
Country
United States
Facility Name
Vertex Investigational Site
City
Kalamazoo
State/Province
Michigan
Country
United States
Facility Name
Vertex Investigational Site
City
St. Louis
State/Province
Missouri
Country
United States
Facility Name
Vertex Investigational Site
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
Vertex Investigational Site
City
Las Vegas
State/Province
Nevada
Country
United States
Facility Name
Vertex Investigational Site
City
Clifton
State/Province
New Jersey
Country
United States
Facility Name
Vertex Investigational Site
City
Freehold
State/Province
New Jersey
Country
United States
Facility Name
Vertex Investigational Site
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
Vertex Investigational Site
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Vertex Investigational Site
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Vertex Investigational Site
City
Hickory
State/Province
North Carolina
Country
United States
Facility Name
Vertex Investigational Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Vertex Investigational Site
City
Bethlehem
State/Province
Pennsylvania
Country
United States
Facility Name
Vertex Investigational Site
City
Duncansville
State/Province
Pennsylvania
Country
United States
Facility Name
Vertex Investigational Site
City
Jackson
State/Province
Tennessee
Country
United States
Facility Name
Vertex Investigational Site
City
Austin
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
Houston
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
Mesquite
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Vertex Investigational Site
City
Clarksburg
State/Province
West Virginia
Country
United States
Facility Name
Vertex Investigational Site
City
Buenos Aires
ZIP/Postal Code
C1121ABE
Country
Argentina
Facility Name
Vertex Investigational Site
City
Buenos Aires
ZIP/Postal Code
C1425EKG
Country
Argentina
Facility Name
Vertex Investigational Site
City
Buenos Aires
ZIP/Postal Code
C1426AAL
Country
Argentina
Facility Name
Vertex Investigational Site
City
Santa Fe
Country
Argentina
Facility Name
Vertex Investigational Site
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Vertex Investigational Site
City
Sevlievo
Country
Bulgaria
Facility Name
Vertex Investigational Site
City
Sofia
ZIP/Postal Code
1233
Country
Bulgaria
Facility Name
Vertex Investigational Site
City
Sofia
ZIP/Postal Code
1784
Country
Bulgaria
Facility Name
Vertex Investigational Site
City
Veliko Tarnovo
ZIP/Postal Code
5000
Country
Bulgaria
Facility Name
Vertex Investigational Site
City
Brno
ZIP/Postal Code
638 00
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Bruntal
ZIP/Postal Code
792 01
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Mlada Boleslav
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Ostrava - Trebovice
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Praha 2
ZIP/Postal Code
760 01
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Zlin
ZIP/Postal Code
760 01
Country
Czech Republic
Facility Name
Vertex Investigational Site
City
Tallinn
ZIP/Postal Code
10117
Country
Estonia
Facility Name
Vertex Investigational Site
City
Tallinn
ZIP/Postal Code
10128
Country
Estonia
Facility Name
Vertex Investigational Site
City
Tallinn
ZIP/Postal Code
11312
Country
Estonia
Facility Name
Vertex Investigational Site
City
Tallinn
ZIP/Postal Code
13419
Country
Estonia
Facility Name
Vertex Investigational Site
City
Koeln
ZIP/Postal Code
50924
Country
Germany
Facility Name
Vertex Investigational Site
City
Leipzig
ZIP/Postal Code
4103
Country
Germany
Facility Name
Vertex Investigational Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Vertex Investigational Site
City
Zerbst
ZIP/Postal Code
39261
Country
Germany
Facility Name
Vertex Investigational Site
City
Baja
ZIP/Postal Code
6500
Country
Hungary
Facility Name
Vertex Investigational Site
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Vertex Investigational Site
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Vertex Investigational Site
City
Szikszó
ZIP/Postal Code
3800
Country
Hungary
Facility Name
Vertex Investigational Site
City
Chihuahua
Country
Mexico
Facility Name
Vertex Investigational Site
City
Cuauhtemoc
Country
Mexico
Facility Name
Vertex Investigational Site
City
San Luis Potos
Country
Mexico
Facility Name
Vertex Investigational Site
City
San Miguel Chapultepec
Country
Mexico
Facility Name
Vertex Investigational Site
City
Bialystok
ZIP/Postal Code
15-879
Country
Poland
Facility Name
Vertex Investigational Site
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Vertex Investigational Site
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Vertex Investigational Site
City
Lublin
ZIP/Postal Code
20-607
Country
Poland
Facility Name
Vertex Investigational Site
City
Poznan
ZIP/Postal Code
60-218
Country
Poland
Facility Name
Vertex Investigational Site
City
Poznan
ZIP/Postal Code
60-539
Country
Poland
Facility Name
Vertex Investigational Site
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Vertex Investigational Site
City
Warszawa
ZIP/Postal Code
00-029
Country
Poland
Facility Name
Vertex Investigational Site
City
Warszawa
ZIP/Postal Code
02-118
Country
Poland
Facility Name
Vertex Investigational Site
City
Warszawa
ZIP/Postal Code
04-141
Country
Poland
Facility Name
Vertex Investigational Site
City
Braila
Country
Romania
Facility Name
Vertex Investigational Site
City
Bucuresti
ZIP/Postal Code
010976
Country
Romania
Facility Name
Vertex Investigational Site
City
Bucuresti
ZIP/Postal Code
011198
Country
Romania
Facility Name
Vertex Investigational Site
City
Judetul Galati
Country
Romania
Facility Name
Vertex Investigational Site
City
Kemerovo
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
Moscow
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
Ryazan
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
St. Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
St. Petersburg
ZIP/Postal Code
191186
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
Yaroslavl
Country
Russian Federation
Facility Name
Vertex Investigational Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Vertex Investigational Site
City
Niska Banja
ZIP/Postal Code
18205
Country
Serbia
Facility Name
Vertex Investigational Site
City
Novi Sad
ZIP/Postal Code
21000
Country
Serbia
Facility Name
Vertex Investigational Site
City
Bratislava
ZIP/Postal Code
84104
Country
Slovakia
Facility Name
Vertex Investigational Site
City
Dunajska Streda
Country
Slovakia
Facility Name
Vertex Investigational Site
City
Poprad
ZIP/Postal Code
5801
Country
Slovakia
Facility Name
Vertex Investigational Site
City
Rimavska Sobota
ZIP/Postal Code
97901
Country
Slovakia
Facility Name
Vertex Investigational Site
City
Donetsk
Country
Ukraine
Facility Name
Vertex Investigational Site
City
Kharkiv
Country
Ukraine
Facility Name
Vertex Investigational Site
City
Lviv
Country
Ukraine
Facility Name
Vertex Investigational Site
City
Odesa
Country
Ukraine
Facility Name
Vertex Investigational Site
City
Vinnytsia
Country
Ukraine

12. IPD Sharing Statement

Learn more about this trial

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

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