A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 12-Month, Multiple-Dose Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of MSDC-0602K in Patients With NASH (EMMINENCE™)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 392
- 主要终点
- Number of Participants With Hepatic Histological Improvement in NAS
研究概览
简要总结
This is a randomized, double-blinded study of three doses of MSDC-0602K or placebo given orally once daily to subjects with biopsy proven NASH with fibrosis and no cirrhosis.
详细描述
This is a randomized, double-blinded study of three doses of MSDC-0602K or placebo given orally once daily to subjects with biopsy proven NASH with fibrosis and no cirrhosis. Visits to the clinic will be at baseline, 1, 2, 3, 6, 9, and 12 months, with one 2- week follow-up visit.
Safety will be assessed by monitoring of vital signs, 12 lead electrocardiogram (ECG), physical examinations, safety labs, and adverse events (AEs).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult subjects 18 years of age or greater
- •Histological evidence of NASH, based on biopsy, with a NAS (NASH CRN scoring) ≥ 4 with a score of at least 1 in each component of NAS.
- •Histological evidence of liver fibrosis defined as NASH CRN System fibrosis score F1 to F
- •Subjects with type 2 diabetes mellitus (DM) must be under stable and reasonable control.
- •Male and female subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 3 months prior to randomization.
- •Females should be either postmenopausal (at least 12 months since last menses) or surgically sterilized (bilateral tubal ligation or hysterectomy). Males with female partners of child-bearing potential must agree to use adequate contraceptive methods (including a condom, plus one other form of contraception) if engaging in sexual intercourse.
- •Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study.
排除标准
- •Known history of HIV.
- •Prior liver transplantation.
- •Other well-documented causes of active chronic liver disease.
- •History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding.
- •History of alcohol abuse or drug abuse within 6 months of Screening.
- •Type 1 diabetes mellitus.
- •Current or history of recent (≤ 6 months) use of ursodeoxycholic acid.
- •Use of concomitant medications with a known significant metabolism by CYP2C8 or CPY2C
- •History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within 6 months prior to randomization.
- •History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to randomization.
- •Blood pressure greater than 160/100 mmHg.
- •Participation in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
- •Malignancy, including leukemia and lymphoma (excluding basal cell and squamous skin cell cancers and localized prostrate cancer) treated within the last 2 years.
研究组 & 干预措施
MSDC-0602K Dose 1 capsules
MSDC-0602K Dose 1 capsule taken once daily for 360 days
干预措施: MSDC-0602K (Drug)
MSDC-0602K Dose 2 capsules
MSDC-0602K Dose 2 capsules taken once daily for 360 days
干预措施: MSDC-0602K (Drug)
MSDC-0602K Dose 3 capsules
MSDC-0602K Dose 3 capsules taken once daily for 360 days
干预措施: MSDC-0602K (Drug)
Placebo capsules
Matching Placebo capsule taken once daily for 360 days
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Hepatic Histological Improvement in NAS
时间窗: 12 months (360 days)
* A decrease of at least 2 points in NAS at 12 months. * At least a 1 point reduction in either ballooning or inflammation from baseline to 12 months. * no increase in CRN fibrosis score (i.e., an increase of 1 stage or more) from baseline to 12 months.
次要结局
- Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months.(12 months (360 days))
- Mean Change From Baseline in NAFLD Activity Score (NAS)(12 months (360 days))
- Mean Change From Baseline in CRN Ballooning Score(12 months (360 days))
- Mean Change From Baseline in CRN Steatosis Score(12 months (360 days))
- Mean Change From Baseline in CRN Inflammation Score(12 months (360 days))
- Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months.(12 months (360 days))
- Mean Change From Baseline in CRN Fibrosis Staging Score(12 months (360 days))