A 12-Week, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Study of Two Doses of VX-702 in Subjects with Moderate to Severe Rheumatoid Arthritis - VeRA

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-000549-13-CZ
• Date of registration: 02/05/2005
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A 12-Week, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Study of Two Doses of VX-702 in Subjects with Moderate to Severe Rheumatoid Arthritis - VeRA
• Scientific title: A 12-Week, Double-Blind, Randomized, Parallel Group, Placebo-Controlled Study of Two Doses of VX-702 in Subjects with Moderate to Severe Rheumatoid Arthritis - VeRA
• Date of first enrolment: 15/06/2005
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-000549-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Czech Republic

Key inclusion & exclusion criteria

Inclusion criteria:
1. Eighteen to 75 years of age
2. Active RA of =6 months in duration as defined by the ACR revised criteria for RA
3. CRP (>2 mg/dL) at the time of randomization
4. Swollen joint count of =8 of 28 and tender joint count of =10 of 28. Joints that have
had prior surgery are to be excluded from the joint count.
5. No prior treatment with DMARD therapy (i.e., DMARD naive) or inadequate
response to DMARD therapy. (Disease modifying anti-rheumatic drugs include oral
or injectable gold, penicillamine, hydroxychloroquine, sulfasalazine, methotrexate, or
leflunomide, please consult the product label for wash out period of leflunomide ). If
the subject has received prior DMARD therapy with an antibody or binding protein to
TNF (anti-TNF), or with recombinant IL-1 receptor antagonist (IL-1Ra), he/she may
have discontinued treatment because of tolerability reasons, but may not have
discontinued treatment because of an inadequate response. Cyclosporin therapy
should have been discontinued for a minimum of 6 month prior to entry into the study
6. If the subject has received treatment with =3 DMARDs, he/she must have
discontinued DMARD therapy (except for sulfasalazine or hydroxychloroquine)
=1 month prior to randomization. Subjects who are receiving a stable dose of
sulfasalazine or hydroxychloroquine for 30 days prior to randomization can remain
on these drugs during the study. Subjects can be switched from another therapy to
sulfasalazine or hydroxychloroquine and be eligible for the study after 1 month at a
stable dose. Subjects must not receive leflunomide or injectable gold for =6 months
prior to randomization, unless an appropriate washout procedure was carried out
(leflunomide).
7. Subjects receiving a nonsteroidal anti-inflammatory drug (NSAID, only one allowed)
and/or prednisone (=10 mg/day) must have been treated at a stable dose(s) for =1
month prior to randomization.
8. Provide informed consent to participate in the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pregnant women or nursing mothers
2. Female subject of childbearing potential who is not using adequate contraception
(defined as use of a barrier method with spermicidal jelly or intrauterine device)
3. Requires concurrent DMARD therapy (other than sulfasalazine or
hydroxychloroquine)
4. Has clinically significant abnormalities in prestudy clinical examination or in
prestudy laboratory test results (including the presence of either hepatitis B surface
antigen or hepatitis C antibody)
5. Requires use of medications that may interfere with study evaluations
6. Has any of the following concurrent medical conditions:
- Uncontrolled diabetes or uncontrolled ischemic heart disease
- Substantial renal impairment (creatinine clearance <40 mL/min, calculated using
the Cockroft-Gault formula)
- History of cancer (with the exception of basal or squamous cell carcinoma of the
skin if adequately treated and no recurrence for >3 years)
- History of liver disease
- History of Torsade de Point and other significant arrhythmia
- Significant active infectious disease requiring systemic antimicrobial therapy,
with the exception of uncomplicated bacterial cystitis in women
- Known positive tuberculin skin test or evidence of tuberculosis by chest X-ray,
without adequate treatment (please consult Appendix I for details)
- Any other concurrent condition which, in the opinion of the investigator, would
preclude participation in or interfere with compliance with the protocol
7. Has elevation in liver function parameters at the Grade 1 toxicity level or higher (i.e., >1.5 × the ULN for ALT, AST, or total bilirubin)
8. Has undergone or is undergoing treatment with another investigational drug or
approved therapy for investigational use within 1 month prior to randomization
9. Has previously participation in this study


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

rheumatoid arthritis

Intervention(s)

Product Code: VX-702
Pharmaceutical Form: Tablet
Current Sponsor code: VX-702
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Current Sponsor code: VX-702
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To define the clinical response to placebo and two doses of VX-702 in subjects with
RA using the number of 20% responses as defined by the American College of
Rheumatology (ACR20) at Week 12 by applying the Jonckheere-Terpstra trend
analysis
- To evaluate the safety and tolerability of 2 dose levels of VX-702 compared to
placebo, when administered for 12 weeks to subjects with RA

Primary end point(s): The primary endpoint for the study is the ACR20 response at Week 12.
An ACR20 response is defined by the following:
• Improvement (reduction) by =20% from baseline in the absolute number of both
swollen and tender joints, and
• Improvement by =20% from baseline in =3 of the following evaluations:
- Physician and subject global assessments of disease
- Subject assessment of pain by visual analog scale (VAS)
- Subject self-assessment of disability (Health Assessment Questionnaire [HAQ])
- Acute phase response as measured by laboratory tests (erythrocyte sedimentation
rate [ESR] or C-reactive protein [CRP]).

Secondary Objective: - To define the clinical response to placebo and two doses of VX-702 in subjects with
RA using the ACR defined 50% and 70% responses (ACR50, 70) over a 12-week
treatment period by applying the Jonckheere-Terpstra trend analysis
- To compare the ACR20 response of individual VX-702 dose groups versus the
placebo group at 12 weeks, by applying pair-wise comparisons
- To define the clinical response to placebo and two doses of VX-702 in subjects with
RA by using the sum of ranks of individual components of the ACR assessment and
the maximum improvements in ACR assessment observed during treatment, by
applying the Jonckheere-Terpstra trend analysis
- To determine the PK and pharmacodynamics (PD) of VX-702 when administered to
subjects with RA for 12 weeks

Secondary ID(s)

VX04-702-301