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

NCT01569152 | Terminated Phase 2 Results

• 4 other identifiers: P08683MK-8457-0082012-000439-17132235
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis (RA)

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12

  ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR20 response is defined as a ≥20% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2) ≥20% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, no pain =0 to extreme pain =100); b) Patient's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100); c) Investigator's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100 ; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from no difficulty =0 to inability to perform tasks =24; and e) serum C-Reactive Protein (decrease indicates improvement). This outcome measure applied to Base Study participants only.

  Week 12

Secondary Outcomes (25)

• Change From Baseline in Disease Activity Score (DAS28) as Measured by Erythrocyte Sedimentation Rate (ESR) at Week 12

  Baseline and Week 12

• Change From Baseline in DAS28 as Measured by C-Reactive Protein (CRP) at Week 12

  Baseline and Week 12

• Percentage of Participants Achieving an ACR70 Response at Week 12

  Week 12

• Percentage of Participants Achieving Hybrid ACR Response at Week 12

  Week 12

• Percentage of Participants Achieving an ACR-N Response at Week 12

  Week 12

Study Arms (3)

Base Study Phase IIa: MK-8457

EXPERIMENTAL

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.

Drug: MK-8457 100 mg; Drug: Methotrexate

Base Study Phase IIa: Placebo

PLACEBO COMPARATOR

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

Drug: Dose-Matched Placebo; Drug: Methotrexate

Safety Extension Period 3: MK-8457

EXPERIMENTAL

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.

Drug: MK-8457 100 mg; Drug: Methotrexate

Interventions

MK-8457 100 mg DRUG

MK-8457 100 mg dosed orally BID

Base Study Phase IIa: MK-8457; Safety Extension Period 3: MK-8457

Dose-Matched Placebo DRUG

Dose-matched placebo dosed orally BID

Base Study Phase IIa: Placebo

Methotrexate DRUG

MTX dosed at the stable dose receive upon study entry

Also known as: MTX

Base Study Phase IIa: MK-8457; Base Study Phase IIa: Placebo; Safety Extension Period 3: MK-8457

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was terminated early (12 September 2013) based on preliminary analysis of data. The results of this study need to be interpreted with caution given the small sample size (82 participants) resulting from the early termination of the study.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinialTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 2, 2012
• Study Start: May 22, 2012
• Primary Completion: October 3, 2013
• Study Completion: October 3, 2013
• Last Updated: March 27, 2019
• Results First Posted: March 9, 2017

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will share