Active rheumatoid arthritis MedDRA version: 16.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: MK-8457
Product Code: MK-8457
Pharmaceutical Form: Capsule
INN or Proposed INN: None
Other descriptive name: MK-8457
Concentration unit: mg milligram(s)
Concentration type: equal
Concent
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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. • Subject must have received MTX for a minimum of 3 months prior to screening with a regionally appropriate stable weekly dose for at least 4 weeks prior to screening (15-25 mg/wk for regions outside of Asia, and 6-25 mg/week for Asia). The subject’s dose of weekly MTX must remain stable through week 24 of the study. • Subject must have either failed treatment with 1 or 2 anti-TNF?therapies or was intolerant to anti-TNF?therapy prior to screening. For subjects who have failed therapy, the treatment with anti-TNF therapies must have been for at least 3 months. Note: The inadequate response or intolerance to anti-TNF therapy will be defined by the Investigator’s assessment and will be recorded. Typically, an inadequate response is based on clinical reasons (e.g., no improvement or worsening of RA). Lack of access to the medication or financial reasons are not considered an inadequate response 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 178 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
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 any biological agents other than anti-TNF therapeutic agents, including but not limited to abatacept, tocilizumab, rituximab or other biological agents used for the treatment of RA. • Subject has received any treatment (listed in the table below) more recently than the indicated washout period prior to randomization. Washout Period for Medications Prior to Randomization Medications, Supplements, and Other Substances Washout Period Prior to Randomization Anti-TNF-a Therapies: Adalimumab Certolizumab Etanercept Golimumab Infliximab 8 weeks 8 weeks 4 weeks 8 weeks 8 weeks Cyclosporine, corticosteroids¹ (parenteral, intra-articular), azathioprine, sulfasalazine, hydroxychloroquine 4 weeks Leflunomide² 8 weeks unless subject undergoes standard cholestyramine or activated charcoal washout in which case 4 weeks washout is required. 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 1 Subjects will be allowed to take stable doses of oral corticosteroids as specified in inclusion criterion #10; i.e., subjects must be on a stable dose of =10 mg prednisone per day (or equivalent) for at least 2 weeks prior to first administration of study medications. 2 Subjects may be allowed to use leflunomide instead of methotrexate on or after Week 24 of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine the effects of MK-8457 100 mg BID compared to placebo over 12 weeks of treatment as measured by ACR20 response. To determine the safety and tolerability of MK-8457 100 mg BID compared to placebo over 12 weeks of treatment.;Secondary Objective: Key Secondary: To determine the effects of MK-8457 100 mg BID compared to placebo as measured by ACR20 at Week 24; DAS28CRP change from baseline at Week 12; and ACR50 at Week 12. - Base Study: To determine the effects of MK-8457 100 mg BID compared to placebo as measured by change from baseline in DAS28CRP at Week 24; ACR50 at Week 24; and HAQ change from baseline at Weeks 12 and 24. Safety Extension: To assess the safety and tolerability of MK-8457 during the safety extension period through Week 100. ;Primary end point(s): • The primary efficacy endpoint is the proportion of subjects achieving ACR20 response at Week 12. The primary safety endpoints are: • Percentage of subjects with adverse experiences; • Change from baseline in laboratory parameters; • Change from baseline in vital signs parameters; • Change in blood pressure from predose to 1 hour, 2 hours and 3 hours after the morning study drug dose at Week 2 and Week 12; and • Average change in blood pressure from predose in the 3 hours time period after am study drug dose at Week 2 and Week 12 ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoints are: • Proportion of subjects achieving ACR20 response at Week 24; • Change from baseline in DAS28CRP at Week 12; and • Proportion of subjects achieving ACR50 response at Week 12. Other secondary efficacy endpoints that will be evaluated include: • Change from baseline in DAS28CRP at Week 24; • Proportion of subjects achieving ACR50 response at Week 24; and • Change from baseline in HAQ at Weeks 12 and 24. Safety endpoints will also be evaluated through Week 100 of the safety extension. ;Timepoint(s) of evaluation of this end point: Weeks 12 and 24 | — |
Countries
Australia, Austria, Brazil, Colombia, Denmark, France, Greece, Hungary, Italy, New Zealand, Peru, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trials Operations (
Merck
Outcome results
None listed