A 12-week, double-blind, randomized, parallel-group, placebo-controlled study of 4 doses of VX-509 in subjects with active rheumatoid arthritis

• Conditions: MedDRA version: 12.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis; active rheumatoid arthritis

• Registration Number: EUCTR2009-017438-32-PL
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-26
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1.Male subjects or female subjects who are confirmed to be of non-childbearing potential, between 18 and 75 years of age (inclusive) on the date of consent who agree on study participation and are able to read, understand, and sign and date a written ICF
2. All subjects must have been diagnosed with RA as defined by the ACR revised criteria (Appendix A), with disease duration of at least 6 months from confirmed diagnosis.
3. 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.
4. Baseline CRP level must be 1.5 times greater than the upper limit of normal at Screening.
5. Subjects must have failed at least 1 nonbiologic DMARD for any reason (please refer to Appendix B for a list of DMARDs). Subjects who have failed previous treatment with MTX must have at least a 1 -month washout period since the last dose of MTX prior to Day 1. Washout periods for other DMARDs are listed in Appendix B.
6. 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. Required washout period from previous biologic DMARD is at least 60 days.
7. Female subjects must be confirmed to be of non-childbearing potential (i.e. either postmenopausal or surgically sterile) in order to be eligible for study enrollment. Female subjects will be considered postmenopausal if they have had 12 months of consecutive spontaneous amenorrhea. A follicle stimulating hormone (FSH) test will be performed locally during the Screening Visit to confirm post-menopausal status. Female subjects will be considered surgically sterile if they are post-hysterectomy, 6 months post surgical bilateral oophorectomy, or 6 months post-tubal ligation .In addition, all females must have a negative serum pregnancy test at the screening visit and also a negative urine pregnancy test at the screening visit and on Day 1 prior to study dosing. Male subjects must be willing to comply with contraception requirements as outlined in Section 12.5.5.1.
8. Subjects must agree not to participate in other interventional clinical studies for the
duration of their participation in this trial.
9. Subjects able to understand and be willing to comply with protocol requirements and instructions and likely to complete the study as planned.
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. Subjects with inflammatory rheumatological disorders other than RA, where arthritis may be a prominent feature, such as systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polydermatomyositis, or Sjogren syndrome, will be excluded. Subjects with RA who have conditions associated secondarily with RA (e.g.,
osteoarthritis of affected joint[s] or sicca syndrome) may be considered for enrollment.
2. Female subjects who are considered to be of childbearing potential (i.e., are not postmenopausal or surgically sterile).
3. Male subjects with female partners that are pregnant, nursing, or planning to become pregnant during the study or within 90 days of the last dose of VX-509.
4. 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.
5. 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 and 2 antibody).
6. Subjects with elevation in alanine aminotransferase or aspartate aminotransferase above the upper limit of normal.
7. History of hematologic disorders including neutropenia and thrombocytopenia.
8. 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.
9. Subjects who have undergone or are undergoing treatment with another investigational drug or approved treatment for investigational use within 3 months or 5 half-lives of the drug, whichever is greater.
10. Subjects who require concomitant use of any inhibitors or inducers of cytochrome P450 (CYP) 3A. Please refer to Appendix C for a partial list of such medications.
1 1. Subjects who have been treated with intra-articular injections of corticosteroids within 28 days prior to Day 1.
12. Subjects who have planned major surgery (e.g., joint replacement) or any procedures during the study.
13. Have received any live, attenuated vaccinations within 1 month prior to study drug
administration. Note: Subjects who receive study drug should not receive any type of
these vaccinations within 1 month after receiving their final dose.
14. History of drug or alcohol abuse or excessive alcohol as determined by the investigator, during the last 12 months before the screening visit.
15.History of TB infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment. Subjects must be screened for TB by customary clinical measures (history, chest x-ray, and skin test) at Screening. Subjects with a PPD skin test with induration >5 mm and <10 mm must have: 1) a negative screening chest radiograph at Screening, 2) a history of Bacille Calmette-Guérin (BCG) vaccination, and 3) a negative serologic test for TB (such as the QuantiFERON or T-spot TB test) in order to be considered eligible for study entry. Subjects with a PPD test 10 mm or greater induration are excluded regardless of BCG va

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified