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

Merck Sharp & Dohme (MSD)

Status and phase

Terminated

Phase 2

Conditions

Rheumatoid Arthritis (RA)

Treatments

Drug: Methotrexate

Drug: MK-8457 100 mg

Drug: Dose-Matched Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT01569152

P08683 (Other Identifier)

MK-8457-008 (Other Identifier)

132235 (Registry Identifier)

2012-000439-17 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

82 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

82 participants in 3 patient groups, including a placebo group

Base Study Phase IIa: MK-8457

Experimental group

Description:

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.

Treatment:

Drug: Methotrexate

Drug: MK-8457 100 mg

Base Study Phase IIa: Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Methotrexate

Drug: Dose-Matched Placebo

Safety Extension Period 3: MK-8457

Experimental group