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 AM3)
This study is currently recruiting participants.
Verified March 2013 by Merck
Sponsor:
Merck
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT01651936
First received: July 25, 2012
Last updated: March 22, 2013
Last verified: March 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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-TNF-α therapy. The primary hypothesis of this study is that among participants with active RA, MK-8457 100 mg BID will be superior to placebo as measured by the proportion of participants who achieve American College of Rheumatology 20 (ACR20) response 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:
Primary Outcome Measures:
- Proportion of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Proportion of Participants Achieving ACR20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
- 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 ]
- Proportion of Participants Achieving American College of Rheumatology 50 (ACR50) Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
- Change From Baseline in DAS28-CRP at Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
- Proportion of Participants Achieving ACR50 Response at Week 24 [ Time Frame: 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 ]
| Estimated Enrollment: | 178 |
| Study Start Date: | August 2012 |
| Estimated Study Completion Date: | October 2015 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: MK-8457
MK-8457 administered orally at a dose of 200 mg daily.
|
Drug: MK-8457
MK-8457 administered orally a t a dose of 100 mg BID for 24 weeks in the base study and an additional 76 weeks in the safety extension; for a combined total of 100 weeks of treatment.
Drug: Methotrexate (MTX)
Participants will continue on the stable dose of MTX that they were receiving prior to study entry.
Other Names:
|
|
Placebo Comparator: Placebo
Matching placebo 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:
Drug: Placebo
Matching placebo administered orally BID.
|
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 received 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
- 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. 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 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 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
- Prior exposure to any biological agents other than anti-TNF therapeutic agents
- Currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 4 weeks prior to screening
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01651936
Show 20 Study Locations
Contacts
| Contact: Toll Free Number | 1-888-577-8839 |
Show 20 Study LocationsSponsors and Collaborators
Merck
More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT01651936 History of Changes |
| Other Study ID Numbers: | 8457-010, 2012-002181-12 |
| Study First Received: | July 25, 2012 |
| Last Updated: | March 22, 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 May 22, 2013