A Phase 2b Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-cirrhotic Nonalcoholic Steatohepatitis.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 183
- 试验地点
- 180
- 主要终点
- Percentage of Participants Who Experienced an Adverse Event (AE)
研究概览
简要总结
This study will evaluate the effect of each dose of MK-3655 versus placebo on the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks. The primary hypothesis of the study is that at least 1 dose of MK-3655 is superior to placebo with respect to the percentage of individuals with NASH resolution without worsening of fibrosis after 52 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has histological confirmation of NASH
- •Is a male or female aged 18 years to 80 years (in Japan and Taiwan aged 20 to 80 years)
- •Has a body mass index (BMI) ≥25 kg/m^2 and ≤50 kg/m^2 and stable weight for the past 3 months
- •Has no history of Type 2 diabetes mellitus (T2DM) OR a history of T2DM controlled by diet or stable doses of antihyperglycemic agents (AHAs)
- •Contraceptive use by male participants should be consistent with local regulations.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and she is not a woman of child-bearing potential (WOCBP) OR she is a WOCBP and uses a contraceptive method that is highly effective during the intervention period and for at least 16 weeks after the last dose of study intervention.
- •Exclusion Criteria
- •Has presence of cirrhosis on liver biopsy
- •Has Type 1 diabetes
- •Has a history of malignancy, unless cancer free ≥5 years, or is under evaluation for active or suspected malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- •Has a history of bariatric surgery ≤5 years before study participation
- •Has undergone a major surgical procedure ≤3 months before study participation or has major surgery planned during the study
- •Has a history or evidence of chronic liver disease other than NASH. Individuals with a history of Hepatitis B or C may be eligible for participation.
- •Has significant systemic or major illnesses other than liver disease, including recent events (≤6 months before study entry) of congestive heart failure, unstable coronary artery disease, arterial revascularization, pulmonary disease, renal failure, stroke, transient ischemic attack, or organ transplantation
排除标准
- 未提供
研究组 & 干预措施
MK-3655 50 mg
Following a 2-week placebo run-in, participants will receive MK-3655 50 mg by subcutaneous (SC) injection once every 4 weeks (Q4W) for 52 weeks.
干预措施: MK-3655 (Drug)
MK-3655 100 mg
Following a 2-week placebo run-in, participants will receive MK-3655 100 mg by SC injection Q4W for 52 weeks.
干预措施: MK-3655 (Drug)
MK-3655 300 mg
Following a 2-week placebo run-in, participants will receive MK-3655 300 mg by SC injection Q4W for 52 weeks.
干预措施: MK-3655 (Drug)
Placebo
Following a 2-week placebo run-in, participants will receive Placebo by SC injection Q4W for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced an Adverse Event (AE)
时间窗: Up to 64 weeks
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Percentage of Participants Discontinuing Study Medication Due to an AE
时间窗: Up to 52 weeks
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study.
Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 52 Weeks
时间窗: Week 52
The NASH Clinical Research Network (CRN) scoring system evaluated by Blinded Independent Central Review (BICR) was used to assess treatment response. The NASH CRN scoring scales were: lobular inflammation score (0-3); hepatocyte ballooning score (0-2); steatosis score (0-3); and fibrosis score (0-4). NASH resolution was defined as a score of 0-1 for inflammation, 0 for ballooning, and any grade of steatosis.
次要结局
- Mean Percent Relative Reduction From Baseline in Liver Fat Content (LFC) After 24 Weeks(Baseline and Week 24)
- Percentage of Participants With ≥2 Point Improvement in NAS With ≥1 Point Improvement in Inflammation or Ballooning Without Worsening of Fbrosis by Histology (Evaluated by BICR) After 52 Weeks(Week 52)
- Percentage of Participants With ≥1 Stage Improvement in Fibrosis Without Worsening of Steatohepatitis Assessed With the NASH CRN Scoring System After 52 Weeks(Week 52)