A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Worldwide, Dose-Ranging Clinical Trial with a Proof-of-Concept Lead Cohort to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 + MTX in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy

• Register: EUCTR
• Last refreshed on: 30 September 2013
• Main ID: EUCTR2012-000439-17-HU
• Date of registration: 20/11/2012
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.
• Public title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Worldwide, Dose-Ranging Clinical Trial with a Proof-of-Concept Lead Cohort to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 + MTX in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy
• Scientific title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Worldwide, Dose-Ranging Clinical Trial with a Proof-of-Concept Lead Cohort to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 + MTX in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy - Proof-of-Concept of MK-8457 in patients with Rheumatoid Arthritis
• Date of first enrolment: 05/02/2013
• Target sample size: 342
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000439-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Adaptive Design If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 6

Countries of recruitment

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

• Name: Holly Weng, M.D.
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.

• Name: Holly Weng, M.D.
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.

Key inclusion & exclusion 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 (15-25 mg/wk for regions outside of Asia, 6–16 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:
•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




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

Health Condition(s) or Problem(s) studied

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

active rheumatoid arthritis

Intervention(s)

Product Name: MK-8457
Product Code: MK-8457
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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 24 weeks of treatment.

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 Outcome(s)

Timepoint(s) of evaluation of this end point: 24 weeks

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.

Secondary ID(s)

8457-008

2012-000439-17-LT

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.