Clinical trial NCT01651936: 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)
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 to Anti-TNF-α Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-07-27
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: In the Base Study, participants were to receive blinded MK-8457 100 mg + MTX or matched placebo + MTX for up to 24 weeks. At Week 12 and 18, efficacy evaluation was conducted to assess eligibility for early escape, defined as \<20% improvement in tender and swollen joint counts. Participants who completed the Base Study and those eligible for early escape could enroll in the 76-week Safety Extension in which participants were to receive open-label MK-8457 100 mg BID + MTX.

All participants must have been treated with MTX for at least 3 months prior to Screening and have been receiving a stable dose of MTX for at least 4 weeks prior to Screening. In addition, each participant must have either failed treatment with 1 or 2 anti-TNF-α therapies or was intolerant to anti-TNF-α therapy prior to Screening. For participants who failed therapy, the treatment with anti-TNF-α therapies must have been for at least 3 months.

Eligibility 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

Primary outcomes:
measure: Change From Baseline in Disease Activity Score (DAS28) as Measured by C-Reactive Protein (CRP) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
timeFrame: Week 12
measure: Percentage of Participants Achieving an ACR20 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving an ACR50 Response at Week 12
timeFrame: Week 12
measure: Change From Baseline in DAS28-CRP at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in the Health Assessment Questionnaire Disability (HAQ Disability Index) at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Achieving an ACR50 Response at Week 24
timeFrame: Week 24
measure: Change From Baseline in the HAQ Disability Index at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: