CTRI/2017/08/009304招募中3 期
A Phase 3, Randomized, Double-Blind, Placebo-Controlled StudyEvaluating the Safety and Efficacy of Selonsertib in Subjects withNonalcoholic Steatohepatitis (NASH) and Bridging (F3) Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 800
- 试验地点
- 20
- 主要终点
- A stratified Mantel-Haenszel (MH) test will be used to compare the differences in proportion of subjects who achieve a ≥ 1-stage
研究概览
简要总结
This is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of SEL in subjects with NASH and bridging (F3) fibrosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Subjects must meet all of the following inclusion criteria to be eligible for participation in this study.
- •Willing and able to give informed consent prior to any study specific procedures being performed 2) Liver biopsy consistent with NASH (defined as the presence of at least grade 1 steatosis, hepatocellular ballooning, and lobular inflammation according to the NAFLD Activity Score [NAS]) and bridging (F3 fibrosis) according to the NASH CRN classification, in the opinion of the central reader.
- •a) historical liver biopsy within 6 months of the Screening visit may be accepted as the Screening biopsy if the sample is deemed acceptable for interpretation by the central reader.
- •b) If the subject is deemed ineligible for this study, the liver biopsy, if performed according to protocol specifications and is within 12 months of the Screening visit, may be used to determine eligibility for study GS-US-384-
- •Subject has the following laboratory parameters at the Screening visit, as determined by the central laboratory: I) ALT ≤ 8 x ULN II) CLcr ≥ 30 mL/min, as calculated by the Cockcroft-Gault equation III) HbA1c ≤ 9.5% IV) Total bilirubin ≤ 1.5 x ULN 4) Body Mass Index (BMI) ≥ 18 kg/m2 at Screening 5) Males and non-pregnant, non-lactating females between 18-70 years of age; inclusive based on the date of the Screening visit 6) Females of childbearing potential (as defined in Appendix 3) must have a negative pregnancy test at Screening and Day 1 7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in.
排除标准
- •Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
- •Prior history of decompensated liver disease, including ascites, HE, or variceal bleeding 2) CP score > 6, as determined at Screening 3) MELD score > 12, as determined at Screening 4) Chronic HBV infection (HBsAg positive) 5) Chronic HCV infection (HCV Ab and HCV RNA positive).
- •Subjects cured of HCV infection less than 5 years prior to the Screening visit are not eligible.
- •Other causes of liver disease including, but not limited to, alcoholic liver disease, hepatitis B, hepatitis C, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, and autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, iron overload, and alpha-1-antitryspin deficiency, based on medical history and centralized review of liver histology.
- •History of liver transplantation 8) Current or history of HCC 9) Any weight reduction surgery in the 2 years prior to Screening or planned during the study (weight reduction surgery is disallowed during the study), and malabsorptive weight loss surgery (e.g., Roux-en-Y or distal gastric bypass) at any time prior to Screening 10) Weight loss > 10% within 6 months of Screening 11) HIV infection (HIV Ab and HIV ribonucleic acid [HIV RNA] positive) 12) Current alcohol consumption greater than 21 oz/week for males or 14 oz/week for females (1oz/30mL of alcohol is present in 1 12oz/360mL beer, 1 4oz/120mL glass of wine, and a 1 oz/30 mL measure of 40 proof alcohol) 13) Positive urine drug screen for amphetamines, cocaine or opiates (i.e. heroin, morphine) at Screening.
- •Subjects on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included in the study.
- •Subjects with a positive urine drug screen due to prescription opioid-based medication are eligible if the prescription and diagnosis are reviewed and approved by the investigator 14) Unstable cardiovascular disease as defined by any of the following: a) Unstable angina, myocardial infarction, coronary artery bypass graft surgery or coronary angioplasty within 6 months prior to Screening b) Transient ischemic attack or cerebrovascular accident within 6 months prior to Screening c) Symptomatic obstructive valvular heart disease or hypertrophic cardiomyopathy d) Congestive heart failure 15) Use of any prohibited concomitant medication as described in Section 5.
- •Subjects on Vitamin E must be on a stable dose for at least 6 months prior to Day 1 and subjects on thiazolidinediones (TZDs) must be on a stable dose for at least 3 months prior to Day 1 16) History of a malignancy within 5 years of Screening with the following exceptions: a) Adequately treated carcinoma in situ of the cervix b) Adequately treated basal or squamous cell cancer or other localized non-melanoma skin cancer 17) Unable to safely undergo a liver biopsy 18) Participation in another investigational study of a drug or device within 30 days or within 5 half-lives of the prior investigational agent (whichever is longer) prior to Screening 19) Concurrent participation in another therapeutic clinical study 20) Known hypersensitivity to SEL, the metabolites, or formulation excipient 21) Any laboratory abnormality or condition that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results 22) Presence of any condition that could, in the opinion of the investigator, compromise the subject’s ability to participate in the study, including a history of substance abuse or a psychiatric condition requiring hospitalization or emergency room visit within 2 years of Screening 23) Unavailable for follow-up assessment or concern for subject’s compliance with the protocol procedures.
结局指标
主要结局
A stratified Mantel-Haenszel (MH) test will be used to compare the differences in proportion of subjects who achieve a ≥ 1-stage
时间窗: Week 48
improvement in fibrosis without worsening of NASH at Week 48 between each of the SEL arms and the placebo arm, adjusting for stratification factors
时间窗: Week 48
次要结局
- Proportion of subjects who have a ≥ 1-stage improvement in fibrosis without worsening of NASH(Week 240)
研究者
研究点 (20)
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