Study of VX-509 in Rheumatoid Arthritis Subjects taking Methotrexate

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2011-004419-22-SK
• Date of registration: 12/04/2012
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Study of VX-509 in Rheumatoid Arthritis Subjects taking Methotrexate
• Scientific 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
• Date of first enrolment: 06/06/2012
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004419-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes 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 Number of treatment arms in the trial: 5

Countries of recruitment

Argentina, Bulgaria, Czech Republic, Estonia, Germany, Hungary, Mexico, Peru, Poland, Romania, Russian Federation, Serbia, Slovakia, Ukraine, United States

Contacts

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female subjects, between 18 and 80 years of age (inclusive)
2. All subjects must have been diagnosed with RA
3. Must have a swollen joint count of =6 out of 66 joints and tender joint count of =6 out of 68 joints
4. Baseline CRP level must be above the upper limit of normal
5. All subjects must have been receiving stable MTX coadministered with folic or folinic acid (at least 5 mg/week)
6. Subjects may remain on 1 nonsteroidal anti-inflammatory medication during the study (aspirin = 325 mg/day is allowed).
7. Subjects must not have received prior treatment with a JAK inhibitor
8. Subjects who are on an additional nonbiologic DMARD (e.g., sulfasalazine) must be willing to discontinue that DMARD after signing consent, except for hydroxcychloroquine
9. Subjects may have received previous therapy with a single TNF inhibitor (e.g., etanercept, adalimumab, infliximab, golimumab, certolizumab pegol)
10. Females must have a negative pregnancy test prior to study dosing
11. Sexually active subjects and their partners must agree to contraceptive requirements

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 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion criteria:
1. 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.
2. Subjects with inflammatory, rheumatological disorders other than RA
3. Pregnant or nursing female subjects
4. Subjects who have a female partner who is pregnant, nursing, or planning to become pregnant
5. Subjects who have planned major surgery (e.g., joint replacement) or procedures during the study
6. History of drug abuse or positive drug screen
7. History of alcohol abuse or excessive alcohol consumption
8. History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.



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

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 15.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: VX-509
Product Code: VX-509
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: VX-509
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 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]

Change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28- CRP) [Time Frame: Week 12]

Safety and tolerability as indicated by adverse events, hematology, clinical chemistry, coagulation, urinalysis, electrocardiograms (ECGs) and vital signs [Time Frame: Week 12]

Timepoint(s) of evaluation of this end point: Week 12

Main Objective: To evaluate the efficacy of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy.

To evaluate the safety and tolerability of multiple doses of VX-509 when administered for 12 weeks in subjects with active RA on stable MTX therapy.

Secondary Objective: To evaluate the efficacy of multiple doses of VX-509 when administered for 24 weeks
To evaluate the safety and tolerability of multiple doses of VX-509 when administered for 24 weeks
To investigate the PK of VX-509 after multiple doses of VX-509 are administered
To investigate the effect of VX-509 on the PK of MTX, after multiple doses of VX-509 are administered
To determine the pharmacodynamic relationships between the exposure of VX-509, MTX, and biomarker responses
To evaluate the durability of efficacy during the OLE
To determine whether subjects who receive their first dose or a higher dose of VX-509 during the OLE attain or increase their level of efficacy
To evaluate the safety and tolerability of chronic administration of VX-509 during the OLE

Secondary Outcome(s)

Secondary end point(s): The primary outcome measures at 24 weeks

Proportion of subjects who achieve ACR50-CRP and ACR70-CRP responses [Time Frame: Week 12 and 24]

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]

Proportion of subjects who achieve remission as defined by DAS28-CRP response [Time Frame: Week 12 and 24]

Proportion of subjects who achieve remission as defined by the ACR/EULAR definition of remission [Time Frame: Week 12 and 24]

Change from baseline in selected Patient Reported Outcomes (PROs) [Time Frame: Week 12 and 24]

Timepoint(s) of evaluation of this end point: Week 12 and 24

Secondary ID(s)

2011-004419-22-DE

VX11-509-102

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated