A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Participants With Rheumatoid Arthritis (MK-8457-010)

NCT ID: NCT01651936

Last Updated: 2021-07-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-29
• Study Completion Date: 2013-10-08

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) and an inadequate response or intolerance to anti-tumor necrosis factor α (anti-TNF-α) therapy. The primary hypothesis of this study is that among participants with active RA, MK-8457 100 mg twice daily (BID) + MTX will be superior to placebo + MTX as measured by the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) after 12 weeks of treatment.

Detailed Description

In the Base Study, participants were to receive blinded MK-8457 100 mg + MTX or matched placebo + MTX for up to 24 weeks. At Week 12 and 18, efficacy evaluation was conducted to assess eligibility for early escape, defined as <20% improvement in tender and swollen joint counts. Participants who completed the Base Study and those eligible for early escape could enroll in the 76-week Safety Extension in which participants were to receive open-label MK-8457 100 mg BID + MTX.

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. In addition, each participant must have either failed treatment with 1 or 2 anti-TNF-α therapies or was intolerant to anti-TNF-α therapy prior to Screening. For participants who failed therapy, the treatment with anti-TNF-α therapies must have been for at least 3 months.

Conditions

Rheumatoid Arthritis

Study Design

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

Study Groups

Base Study: MK-8457

Participants received MK-8457 100 mg dosed twice daily (BID) orally with MTX at the stable dose received upon study enrollment. The Base Study 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 received upon study entry

Base Study: Placebo

Participants received placebo BID orally with MTX at the stable dose received upon study enrollment. The Base Study lasted up to 24 weeks.

Group Type: PLACEBO_COMPARATOR

Methotrexate

Intervention Type: DRUG

MTX dosed at the stable dose received upon study entry

Dose-match placebo

Intervention Type: DRUG

Dose-matched placebo dosed orally BID

Safety Extension: MK-8457

Participants received MK-8457 100 mg dosed twice daily (BID) orally with MTX at the stable dose received upon study enrollment. The Safety Extension was to last up to 76 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 received upon study entry

Interventions

MK-8457 100 mg

MK-8457 100 mg dosed orally BID

Intervention Type: DRUG

Methotrexate

MTX dosed at the stable dose received upon study entry

Intervention Type: DRUG

Dose-match placebo

Dose-matched placebo dosed orally BID

Intervention Type: DRUG

Other Intervention Names

Rheumatrex; Trexall

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 or an elevated erythrocyte sedimentation rate (ESR) >28 mm/hr and evidence of synovitis on imaging
• 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. The dose of methotrexate must remain stable through Week 24 of the study.
• Failed treatment with 1 or 2 anti-tumor necrosis factor alpha (anti-TNF-α) therapies or was intolerant to anti-TNF-α therapy prior to screening
• If using non-steroidal anti-inflammatory drugs or other analgesics, participant must be on a stable dose
• No history of either untreated latent or active tuberculosis (TB) 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
• Hospitalization due to an acute cardiovascular event, cardiovascular illness, or cardiovascular surgery within 6 months of screening
• Participant has a transplanted organ, excluding corneal transplant, performed > 3 months prior to the first dose of trial medication
• History of, or current ongoing ,chronic or recurrent infectious disease
• Positive hepatitis B surface antigen or hepatitis C test result
• Human immunodeficiency virus (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
• Prior exposure to fostamatinib or other spleen tyrosine kinase inhibitors
• Prior exposure to 3 or more anti-TNF therapeutic agents
• Has been treated for RA with a marketed biologic agent (other than anti-TNF therapeutic agents) and failed the agent due to lack of efficacy
• Currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 4 weeks prior to screening
• Severe opportunistic infection within the 6 months prior to screening

• 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

2012-002181-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8457-010

Identifier Type: -

Identifier Source: org_study_id