active rheumatoid arthritis
Conditions
Interventions
Product Name: MK-8457
Product Code: MK-8457
Pharmaceutical Form: Tablet
INN or Proposed INN: None
Other descriptive name: MK-8457
Concentration unit: mg milligram(s)
Concentration type: equal
Concentr
Sponsors
MERCK SHARP & DOHME CORP.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subject must be =18 years of age on the day of signing the informed consent. RA diagnosis and disease activity: • Subject has a diagnosis of RA for at least 6 months prior to screening. • Subject has active RA as defined by the presence of 6 swollen joints (of 66 joint count) AND 6 tender joints (of 68 joint count) at screening (Visit 1) and baseline (Visit 2). • Subject has a C-reactive protein (CRP) blood level > 0.9 mg/dL from the central reference laboratory at screening. • Subject is anti-cyclic citrullinated antibody positive and/or rheumatoid factor positive at screening. • Subject is ACR functional Class I, II, or III. • Subjects has received MTX for a minimum of 3 months with a regionally appropriate stable weekly dose (7.25-25 mg/wk for regions outside of Asia, 6–25 mg/week for Asia) for at least 4 wks prior to entering 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 419 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • Subject has inflammatory disease other than RA, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease. • Previous exposure to fostamatinib or other splenic tyrosine kinase (SYK) inhibitors. • Previous exposure to TNF-alpha targeted therapy or any biological agents for RA. • Subject has received any treatment listed below more recently than the indicated washout period prior to Screening. Prohibited Medications, Supplements, and Other Substances Washout Period Prior to Screening Disease modifying anti-rheumatic drugs such as but not limited to (not including cytotoxic agents): Leflunomide, cyclosporine, mycophenolate mofetil, azathioprine, corticosteroids (parenteral, intra-articular), sulfasalazine, hydroxychloroquine 30 days (8 weeks for leflunomide unless subject undergoes standard cholestyramine or activated charcoal washout) Cytotoxic agents including chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents 3 months Live vaccinations 1 month Investigational medications 30 days or 5 half lives of the investigational agent whichever is longer Bacille Calmette-Guerin (BCG) vaccination 1 month
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the optimal dose of MK-8457 + MTX as compared to placebo + MTX, as demonstrated the RA subjects who achieve ACR20 (American College of Rheumatology 20) response after 12 weeks of treatment.;Secondary Objective: To determine the effects of 24 weeks of treatment with MK-8457 100 mg BID + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, ACR-N, change from baseline in individual ACR components, DAS28CRP, DAS28ESR (DAS28 response, DAS28 remission, and change from baseline) DAS-AUC, Simplified Disease Activity Index (SDAI), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), change from baseline in Hemoglobin; (2) To determine the effects of 24 weeks of treatment with all other doses of MK-8457 + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, and change from baseline in individual ACR components, DAS28, SDAI, ESR, CRP, SF-36, HAQ, and FACIT-F.;Primary end point(s): American College of Rheumatology 20 (ACR20) response at 24 weeks ;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective: To determine the effects of 24 weeks of treatment with MK-8457 100 mg BID + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, ACR-N, change from baseline in individual ACR components, DAS28CRP, DAS28ESR (DAS28 response, DAS28 remission, and change from baseline) DAS-AUC, Simplified Disease Activity Index (SDAI), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Short Form Health Survey (SF-36), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), change from baseline in Hemoglobin (2) Objective: To determine the effects of 24 weeks of treatment with all other doses of MK-8457 + MTX compared to placebo (PBO) + MTX on the following endpoints: ACR50, ACR70, hybrid ACR response, and change from baseline in individual ACR components, DAS28, SDAI, ESR, CRP, SF-36, HAQ, and FACIT-F. ;Timepoint(s) of evaluation of this end point: 24 weeks | — |
Countries
Brazil, Canada, Chile, Denmark, Germany, Hungary, India, Japan, Korea, Democratic People's Republic of, Latvia, Lithuania, Mexico, Moldova, Republic of, Peru, Poland, Russian Federation, South Africa, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Department
UAB "Merck Sharp & Dohme"
Outcome results
None listed