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)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01651936
First received: July 25, 2012
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the safety and efficacy of MK-8457 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) will be superior to placebo as measured by the change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) after 12 weeks of treatment.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: MK-8457
Drug: Methotrexate (MTX)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Worldwide, Proof-of-Concept Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of MK-8457 in Subjects With Active Rheumatoid Arthritis and an Inadequate Response or Intolerance for Anti-TNF-α Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in the Disease Activity Score 28 C-Reactive Protein (DAS28-CRP) at Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Participants Achieving American College of Rheumatology 20 (ACR20) Response at at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Proportion of Participants Achieving ACR20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of Participants Achieving ACR50 Response at Week 12 and Week 24 [ Time Frame: Week 12, Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in DAS28-CRP at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Health Assessment Questionnaire (HAQ) at Week 12 and Week 24 [ Time Frame: Baseline, Week 12, Week 24 ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: August 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
MK-8457 administered orally at a dose of 100 mg twice daily (BID) for 24 weeks in the base study and an additional 76 weeks in the safety extension study; for a combined total of 100 weeks of treatment.
Drug: MK-8457
MK-8457 administered orally at a dose of 200 mg daily.
Drug: Methotrexate (MTX)
Participants will continue on the stable dose of MTX that they were receiving prior to study entry.
Other Names:
  • Rheumatrex
  • Trexall
Placebo Comparator: Placebo
Matching placebo to MK-8457 administered orally BID.
Drug: Methotrexate (MTX)
Participants will continue on the stable dose of MTX that they were receiving prior to study entry.
Other Names:
  • Rheumatrex
  • Trexall
Drug: Placebo
Matching placebo to MK-8457 administered orally.

Detailed Description:

This study consists of a 24-week base study in which participants will receive MK-8457 100 mg twice daily or matching placebo, and a 76-week safety extension in which participants will receive MK-8457 100 mg twice daily.

  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 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
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01651936     History of Changes
Other Study ID Numbers: 8457-010, 2012-002181-12
Study First Received: July 25, 2012
Last Updated: October 25, 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 April 16, 2014