Safety and Efficacy of MK-8457 and Methotrexate (MTX) in Participants With Active Rheumatoid Arthritis Despite MTX Therapy (P08683, MK-8457-008)

NCT ID: NCT01569152

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-22
• Study Completion Date: 2013-10-03

Brief Summary

The purpose of this study is to assess the safety and efficacy of MK-8457 + Methotrexate (MTX) in participants with active rheumatoid arthritis (RA) despite MTX therapy. The primary hypothesis is that at least 1 dose of MK-8457 + MTX will be superior to placebo + MTX as measured by the percentage of participants who achieve American College of Rheumatology 20 (ACR 20) response after 12 weeks of treatment.

Detailed Description

In Base Study Phase IIa, participants were to receive blinded MK-8457 100 mg or matched placebo for up to 24 weeks. At Week 12 and 18 of Phase IIa, efficacy evaluation was conducted to assess eligibility for early escape, defined as <20% reduction in both tender and swollen joint counts. The study plan included Base Study Phase IIb in which dose range finding or dose-response was to be evaluated, depending on the outcome of Phase IIa. Participants who completed Phase IIa or Phase IIb and those eligible for early escape could enroll in Period 3, a 2-year Safety Extension.

All participants must have been treated with MTX for at least 3 months prior to screening and have been receiving a stable dose of MTX for at least 4 weeks prior to screening.

Conditions

Rheumatoid Arthritis (RA)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Base Study Phase IIa: MK-8457

Participants received MK-8457 100 mg dosed twice daily (BID) orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.

Group Type: EXPERIMENTAL

MK-8457 100 mg

Intervention Type: DRUG

MK-8457 100 mg dosed orally BID

Methotrexate

Intervention Type: DRUG

MTX dosed at the stable dose receive upon study entry

Base Study Phase IIa: Placebo

Participants received placebo dosed BID orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.

Group Type: PLACEBO_COMPARATOR

Dose-Matched Placebo

Intervention Type: DRUG

Dose-matched placebo dosed orally BID

Methotrexate

Intervention Type: DRUG

MTX dosed at the stable dose receive upon study entry

Safety Extension Period 3: MK-8457

Participants received MK-8457 100 mg BID orally with MTX at the stable dose received upon study enrollment. Period 3 was to last up to 2 years.

Group Type: EXPERIMENTAL

MK-8457 100 mg

Intervention Type: DRUG

MK-8457 100 mg dosed orally BID

Methotrexate

Intervention Type: DRUG

MTX dosed at the stable dose receive upon study entry

Interventions

MK-8457 100 mg

MK-8457 100 mg dosed orally BID

Intervention Type: DRUG

Dose-Matched Placebo

Dose-matched placebo dosed orally BID

Intervention Type: DRUG

Methotrexate

MTX dosed at the stable dose receive upon study entry

Intervention Type: DRUG

Other Intervention Names

MTX

Eligibility Criteria

Inclusion Criteria

• Diagnosis of rheumatoid arthritis for at least 6 months prior to screening
• Active rheumatoid arthritis as defined by the presence of >= 6 swollen joints (of 66 count) and >= 6 tender joints (of 68 joint count)
• C-reactive protein blood level >0.9 mg/dL
• Anti-citrullinated protein antibody positive and/or rheumatoid factor positive at screening
• American College of Rheumatology Functional Class I, II, or III
• Received methotrexate for a minimum of 3 months prior to screening with a regionally appropriate stable weekly dose for at least 4 weeks prior to screening
• If using oral corticosteroids, the participant must be on a stable dose of 10 mg prednisone
• No history of either untreated, latent, or active tuberculosis prior to baseline
• Participants of reproductive potential must agree to remain abstinent or use 2 acceptable methods of birth control

Exclusion Criteria

• Presence of inflammatory disease other than rheumatoid arthritis, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or Lyme disease
• Positive hepatitis B surface antigen or hepatitis C test result or the presence of Human immunodeficiency virus (HIV) infection
• HIV positive
• User of recreational or illicit drugs or has had a history (within the previous 2 years) of drug or alcohol abuse or dependence
• Females of childbearing potential who are pregnant, intend to become pregnant, or are lactating;
• Severe opportunistic infection within 6 months prior to study start.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

MK-8457-008

Identifier Type: OTHER

Identifier Source: secondary_id

2012-000439-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

132235

Identifier Type: REGISTRY

Identifier Source: secondary_id

P08683

Identifier Type: OTHER

Identifier Source: secondary_id

P08683

Identifier Type: -

Identifier Source: org_study_id