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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 82
- 主要终点
- Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of MK-8457 + Methotrexate (MTX) in participants 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 percentage of participants who achieve American College of Rheumatology 20 (ACR 20) response after 12 weeks of treatment.
详细描述
In Base Study Phase IIa, participants were to receive blinded MK-8457 100 mg or matched placebo for up to 24 weeks. At Week 12 and 18 of Phase IIa, efficacy evaluation was conducted to assess eligibility for early escape, defined as <20% reduction in both tender and swollen joint counts. The study plan included Base Study Phase IIb in which dose range finding or dose-response was to be evaluated, depending on the outcome of Phase IIa. Participants who completed Phase IIa or Phase IIb and those eligible for early escape could enroll in Period 3, a 2-year Safety Extension.
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Base Study Phase IIa: MK-8457
Participants received MK-8457 100 mg dosed twice daily (BID) orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.
干预措施: Methotrexate (Drug)
Base Study Phase IIa: MK-8457
Participants received MK-8457 100 mg dosed twice daily (BID) orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.
干预措施: MK-8457 100 mg (Drug)
Base Study Phase IIa: Placebo
Participants received placebo dosed BID orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.
干预措施: Dose-Matched Placebo (Drug)
Base Study Phase IIa: Placebo
Participants received placebo dosed BID orally with MTX at the stable dose received upon study enrollment. Phase IIa lasted up to 24 weeks.
干预措施: Methotrexate (Drug)
Safety Extension Period 3: MK-8457
Participants received MK-8457 100 mg BID orally with MTX at the stable dose received upon study enrollment. Period 3 was to last up to 2 years.
干预措施: MK-8457 100 mg (Drug)
Safety Extension Period 3: MK-8457
Participants received MK-8457 100 mg BID orally with MTX at the stable dose received upon study enrollment. Period 3 was to last up to 2 years.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
时间窗: Week 12
ACR responses are numerical measurements of improvement in multiple disease assessment criteria. An ACR20 response is defined as a ≥20% improvement in 1) swollen joint count (66 joints) and tender joint count (68 joints) (0 = Absent; 1 = Present) and 2) ≥20% improvement in 3 of the following 5 assessments: a) a participant's overall assessment of pain on a visual analog scale (VAS, no pain =0 to extreme pain =100); b) Patient's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100); c) Investigator's Global Assessment of Disease Activity VAS (doing very well =0 to doing very poor =100 ; d) participant's assessment of function across 8 functional areas as measured by Health Assessment Questionnaire (HAQ), total scores ranging from no difficulty =0 to inability to perform tasks =24; and e) serum C-Reactive Protein (decrease indicates improvement). This outcome measure applied to Base Study participants only.
次要结局
- Change From Baseline in DAS28 as Measured by C-Reactive Protein (CRP) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving a DAS28-ESR Response at Week 12(Week 12)
- Change From Baseline in Disease Activity Score (DAS28) as Measured by Erythrocyte Sedimentation Rate (ESR) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving a DAS28-CRP Response at Week 12(Week 12)
- Percentage of Participants Achieving DAS28-ESR Remission at Week 12(Week 12)
- Percentage of Participants Achieving DAS28-CRP Remission at Week 12(Week 12)
- DAS28-ESR Area Under the Curve (AUC)(Up to 12 weeks)
- DAS28-CRP Area Under the Curve (AUC)(Up to 12 weeks)
- Change From Baseline in Tender Joint Count at Week 12(Baseline and Week 12)
- Change From Baseline in Swollen Joint Count at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving an ACR70 Response at Week 12(Week 12)
- Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12(Baseline and Week 12)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 12(Baseline and Week 12)
- Change From Baseline in the Health Assessment Questionnaire Disability (HAQ Disability Index) at Week 12(Baseline and Week 12)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving Hybrid ACR Response at Week 12(Week 12)
- Percentage of Participants Achieving an ACR-N Response at Week 12(Week 12)
- Change From Baseline in the Short Form Health Survey (SF-36) at Week 12(Baseline and Week 12)
- Change From Baseline in the Patient's Global Assessment of Disease Status/Activity (PGADSA) at Week 12(Baseline and Week 12)
- Change From Baseline in the Investigator's Global Assessment of Disease Status/Activity (IGADSA) at Week 12(Baseline and Week 12)
- Change From Baseline in the Patient's Global Assessment of Pain (PGAP) at Week 12(Baseline and Week 12)
- Change From Baseline in Serum C-Reactive Protein (CRP) at Week 12(Baseline and Week 12)
- Change From Baseline in Hemoglobin at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving an ACR50 Response at Week 12(Week 12)
- Percentage of Participants With an ACR20 Response Over Time(Week 1, Week 2, Week 4, Week 6, Week 18 and Week 24)