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)

NCT01651936 | Terminated Phase 2 Results

• 2 other identifiers: 8457-0102012-002181-12
• Study Type: interventional
• Target: 56
• 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) 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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

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

  The DAS28-CRP is a continuous parameter based upon a statistically-derived index combining tender joints (28 joints; 0=absent, 1=present; TEN28), swollen joints (28 joints; 0=absent, 1=present; SW28), CRP (an inflammatory marker, decrease indicates improvement), and Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) (0=doing very well to 100=doing very poor; GH). It is defined as follows: DAS28-CRP = 0.56 × SQRT(TEN28) + 0.28 × SQRT(SW28) + 0.36 × ln (CRP+1) + 0.014 × GH + 0.96. The DAS28-CRP is a scale ranging from 0 to 10 with higher values indicating greater RA disease activity. This outcome measure applied to Base Study participants only.

  Baseline and Week 12

Secondary Outcomes (7)

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

  Week 12

• Percentage of Participants Achieving an ACR20 Response at Week 24

  Week 24

• Percentage of Participants Achieving an ACR50 Response at Week 12

  Week 12

• Change From Baseline in DAS28-CRP at Week 24

  Baseline and Week 24

• Change From Baseline in the Health Assessment Questionnaire Disability (HAQ Disability Index) at Week 12

  Baseline and Week 12

Study Arms (3)

Base Study: MK-8457

EXPERIMENTAL

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.

Drug: MK-8457 100 mg; Drug: Methotrexate

Base Study: Placebo

PLACEBO COMPARATOR

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

Drug: Methotrexate; Drug: Dose-match placebo

Safety Extension: MK-8457

EXPERIMENTAL

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.

Drug: MK-8457 100 mg; Drug: Methotrexate

Interventions

MK-8457 100 mg DRUG

MK-8457 100 mg dosed orally BID

Base Study: MK-8457; Safety Extension: MK-8457

Methotrexate DRUG

MTX dosed at the stable dose received upon study entry

Also known as: Rheumatrex, Trexall

Base Study: MK-8457; Base Study: Placebo; Safety Extension: MK-8457

Dose-match placebo DRUG

Dose-matched placebo dosed orally BID

Base Study: Placebo

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 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

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
• 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

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 (56 participants) resulting from 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: July 25, 2012
• First Posted: July 27, 2012
• Study Start: August 29, 2012
• Primary Completion: October 8, 2013
• Study Completion: October 8, 2013
• Last Updated: July 30, 2021
• Results First Posted: February 23, 2017

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share