Rheumatoide arthritis.
Conditions
Interventions
Subjects with active rheumatoid arthritis (RA) were enrolled in a randomized double-blind, placebo-controlled, parallel-group study exposed to either SCH 351125 50 mg BID or matched placebo, in a 2:1
Sponsors
Schering Plough Research Institute, Kenilworth, NJ
Eligibility
Inclusion criteria
Inclusion criteria: 1. Subjects 18 to 70 years of age, of either sex, and of any race; 2. Diagnosis of RA according to the American College of Rheumatology (ACR) criteria, for at least 6 weeks prior to entry in the study (see Appendix 6); 3. Active RA defined as: three or more tender joints, three or more swollen joints and at least one of the following three: a. duration of morning stiffness equal to or greater than 45 minutes; b. erythrocyte sedimentation rate equal to or greater than 28 mm/hr; c. or C-reactive protein equal to or greater than 10 mg/L; 4. Functional Class I, II or III (see Appendix 6); 5. Subjects must be free of any clinically significant disease (other than rheumatoid arthritis) that would interfere with the study evaluations and/or safety; 6. Subjects must be willing to give written informed consent and able to adhere to dose and visit schedules; 7. Females must not be breast-feeding, and either be of nonchildbearing potential (ie, sterilized via hysterectomy or bilateral tubal ligation or at least 1 year postmenopausal) or if of child bearing potential, must be practicing effective double barrier contraceptive methods from at least 2 weeks prior to Day 1 and until 30 days following cessation of dosing; 8. Female subjects of childbearing potential must have a negative serum pregnancy test (beta-hCG) at Screening; 9. Males must practice an effective barrier method of contraception from Day 1 until 30 days following cessation of dosing; 10. A physical examination must be without clinically significant findings with exception of those finding related to rheumatoid arthritis; 11. At Screening, ECG conduction intervals must be within the gender specific normal range (ie, QTc for males <430 msec and females <450 msec).
Exclusion criteria
Exclusion criteria: 1. Individuals with a history of any significant medical disorder which require a physician's care (excluding rheumatoid arthritis) and would interfere with the study evaluations or compromise subject safety; 2. Individuals who have a history of any clinically significant local or systemic infectious disease within four weeks prior to drug administration; 3. Any subject with an allergy to gadolinium; 4. Any subject with a pacemaker, metal object implanted their body or any other device or condition which may interfere with a subject’s safety during the MRI procedure; 5. Any subject who has received DMARD treatment within 30 days prior to enrollment (leflunomide requires a charcoal or cholestyramine washout); 6. Any subject who has received anti-TNF therapy (except enteracept) or any biologic therapy within the previous 90 days; 7. Any subject whose baseline disease activity score (DAS28) (Appendix 6) has significantly changed since screening to indicate unstable disease; 8. Any individual who does not comply with the requirement that he should not have used; any drugs (including herbal and mineral supplements or vitamins), other than acetaminophen or an approved stable regimen of low dose prednisone (10 mg/day) and/or NSAIDS, for at least two weeks prior to study drug administration; alcohol in amounts of greater than 50 grams a day throughout the study; 9. Subjects that have been diagnosed with Juvenile RA (see Appendix 11); 10. A history of systemic lupus erythematosus, or signs and symptoms suggesting systemic lupus erythematosus; 11. Subjects who are positive for hepatitis B surface antigen, hepatitis C RNA or for HIV antibodies; 12. Individuals who have participated in a clinical trial of an investigational drug within 90 days prior to the start of study drug administration, or have received prior treatment with a CCR5 receptor antagonist; 13. Individuals with a positive screen for drugs of abuse; 14. Individuals who have donated blood (>300 mL) within the preceding 90 days; 15. Males who are unwilling to use/practice an effective method of contraception (ie, condom in conjunction with spermicide from study start until 30 days after the last study treatment; 16. Females who are unwilling to use/practice an effective method of contraception (ie, condom in conjunction with spermicide from 2 weeks prior to study start until 30 days after the last study treatment; 17. Individuals who have received any vaccinations within 30 days prior to Screening; 18. Individuals with any clinically significant history of food or drug allergy or allergy to any component of SCH 351125; 19. Subjects who are not willing to follow the study restrictions or procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To determine the effects of SCH 351125, a CCR5 receptor antagonist, on mononuclear cell migration into synovial tissue in subjects with rheumatoid arthritis; 2. to evaluate the safety and tolerability of multiple-dose administration of SCH 351125 50 mg twice-daily in subjects with rheumatoid arthritis when administered for 28 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To explore the effects of SCH 351125 on: a. Synovial inflammation via MRI; b. chemokine expression and concentrations in the plasma, synovial tissue and synovial fluid (mRNA expression only); c. mononuclear cell concentrations in the peripheral blood; d. clinical signs and symptoms of rheumatoid arthritis and to; e. determine the single-dose and multiple dose pharmacokinetic profile of SCH 351125 in subjects with rheumatoid arthritis. | — |
Contacts
Public ContactP.P. Tak
Academic Medical Center (AMC), Department of Clinical Immunology and Rheumatology, P.O. Box 22660
Outcome results
None listed