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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01569152
First received: March 30, 2012
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the safety and efficacy of MK-8457 + Methotrexate (MTX) in subjects 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 proportion of subjects who achieve American College of Rheumatology 20 (ACR 20) response after 12 weeks of treatment.


Condition Intervention Phase
Rheumatoid Arthritis (RA)
Drug: MK-8457 100 mg BID
Drug: Dose-Matched Placebo
Drug: MK-8457 150 mg QD
Drug: MK-8457 75 mg QD
Drug: MK-8457 25 mg QD
Drug: MTX
Drug: MK-8457 25 mg BID
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Participant American College of Rheumatology (ACR) 20 Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Disease Activity Score (DAS-28) as Measured by Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in DAS-28 as Measured by C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant ACR70 Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant Hybrid ACR Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant ACR-N Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant DAS-28 ESR Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant DAS-28 CRP Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant DAS-28 ESR Remission [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant DAS-28 CRP Remission [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant DAS-28 Area Under the Curve (AUC) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant Change from Baseline in Tender Joint Count [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant Change from Baseline in Swollen Joint Count [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant Change from Baseline in the Simplified Disease Activity Index (SDAI) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant Change from Baseline in the Short Form Health Survey (SF-36) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant Change from Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Patient's Global Assessment of Disease Status/Activity [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Investigator's Global Assessment of Disease Status/Activity [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Patient's Global Assessment of Pain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in the Health Assessment Questionnaire Disability Subscales [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in Serum CRP [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in ESR [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in Hemoglobin [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
  • Participant ACR50 Response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Participant ACR20 Response Over Time [ Time Frame: Baseline, Week 1, Week 2, Week 5, Week 6, Week 18 ] [ Designated as safety issue: No ]

Enrollment: 82
Study Start Date: May 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8457 100 mg BID + MTX Phase 2a
Participants will receive MK-8457 100 mg dosed twice daily (BID) orally with methotrexate at the stable dose received upon study enrollment.
Drug: MK-8457 100 mg BID
MK-8457 100 mg dosed orally twice daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Placebo Comparator: Placebo + MTX Phase 2a
Participants will receive placebo dosed twice daily (BID) orally with methotrexate at the stable dose received upon study enrollment.
Drug: Dose-Matched Placebo
Dose-matched placebo dosed orally.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Experimental: MK-8457 100 mg BID + MTX Phase 2b
Participants will receive MK-8457 100 mg dosed twice daily (BID) orally with methotrexate at the stable dose received upon study enrollment.
Drug: MK-8457 100 mg BID
MK-8457 100 mg dosed orally twice daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Experimental: MK-8457 150 mg QD + MTX Phase 2b
Participants will receive MK-8457 150 mg dosed once daily (QD) orally with methotrexate at the stable dose received upon study enrollment.
Drug: MK-8457 150 mg QD
MK-8457 dosed orally once daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Experimental: MK-8457 75 mg QD + MTX Phase 2b
Participants will receive MK-8457 75 mg dosed once daily (QD) orally with methotrexate at the stable dose received upon study enrollment.
Drug: MK-8457 75 mg QD
MK-8457 dosed orally once daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Experimental: MK-8457 25 mg BID + MTX Phase 2b
Participants will receive MK-8457 25 mg dosed twice daily (BID) orally with methotrexate at the stable dose received upon study enrollment. This dose was removed from the study by amendment 07.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Drug: MK-8457 25 mg BID
MK-8457 25 mg dosed orally twice daily
Experimental: MK-8457 25 mg QD + MTX Phase 2b
Participants will receive MK-8457 25 mg dosed once daily (QD) orally with methotrexate at the stable dose received upon study enrollment.
Drug: MK-8457 25 mg QD
MK-8457 25 mg dosed orally once daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Placebo Comparator: Placebo + MTX Phase 2b
Participants will receive dose-matched placebo tablets plus methotrexate at the stable dose received upon study enrollment.
Drug: Dose-Matched Placebo
Dose-matched placebo dosed orally.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.
Experimental: MK-8457 Safety Extension
Participants in the safety extension will receive active treatment with MK-8457.
Drug: MK-8457 100 mg BID
MK-8457 100 mg dosed orally twice daily.
Drug: MK-8457 150 mg QD
MK-8457 dosed orally once daily.
Drug: MK-8457 75 mg QD
MK-8457 dosed orally once daily.
Drug: MK-8457 25 mg QD
MK-8457 25 mg dosed orally once daily.
Drug: MTX
MTX dosed at the stable dose receive upon study entry.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01569152     History of Changes
Other Study ID Numbers: P08683, MK-8457-008, 2012-000439-17
Study First Received: March 30, 2012
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014