Companion Protocol for the ¹³C-Methacetin Breath Test Using the BreathID® MCS System for Conatus Phase 2 Study of Emricasan, an Oral Caspase Inhibitor, Under Protocol IDN-6556-14 (NCT02960204)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 343
- 试验地点
- 1
- 主要终点
- Number of Subjects With Matched Clinically Significant Portal Hypertension Based on Hepatic Venous Pressure Gradient (HVPG) and Methacetin Breath Test (MBT)
研究概览
简要总结
To validate the ability of the Methacetin Breath Test (MBT) to detect clinically significant portal hypertension (CSPH)/severe portal hypertension (SPH) defined as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg and HVPG ≥ 12 mmHg respectively, in patients with non-alcoholic steatohepatitis (NASH) during the course of treatment with Conatus's investigational product emricasan/placebo.
详细描述
This study is a companion protocol that will use the data generated by Conatus' study of emricasan under protocol IDN-6556-14 (NCT02960204).The IDN-6556-14 study is a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial in subjects with non-alcoholic steatohepatitis (NASH) cirrhosis and severe portal hypertension.
As one of the Conatus' study exploratory objectives, this companion protocol is designed to assess whether emricasan compared to placebo improves liver metabolic function at Weeks 24 and 48 as assessed by the methacetin breath test (at select sites), if relevant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The collaborator is responsible for the masking process.
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
- •Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
- •Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
- •Compensated cirrhosis OR Decompensated cirrhosis with no more than 1 prior significant decompensating event.
- •Severe portal hypertension defined as HVPG ≥12 mmHg
- •Subjects who are on NSBB, nitrates, diuretics, lactulose, rifaximin, or statins must be on a stable dose for at least 3 months prior to Day 1
- •Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug
排除标准
- •Evidence of severe decompensation
- •Severe hepatic impairment defined as a Child-Pugh score ≥10
- •ALT >3 times upper limit of normal (ULN) or AST >5 times ULN during screening
- •Estimated creatinine clearance <30 mL/min
- •Prior transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure
- •Known portal vein thrombosis
- •Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy, other definitive treatment (e.g. sphincterotomy), or medical management (e.g. ursodeoxycholic acid)
- •Current use of medications that are considered inhibitors of OATP1B1 and OATP1B3 transporters
- •Alpha-fetoprotein >50 ng/mL
- •History or presence of clinically concerning cardiac arrhythmias, or prolongation of screening (pre-treatment) QTcF interval of >500 msec
- •History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
- •Prior liver transplant
- •Change in diabetes medications or vitamin E within 3 months of screening
- •Uncontrolled diabetes mellitus (HbA1c >9%) within 3 months of screening
- •Significant systemic or major illness other than liver disease
- •HIV infection
- •Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening
- •If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
- •Previous treatment with emricasan or active investigational medication (except methacetin) in a clinical trial within 3 months prior to Day 1
研究组 & 干预措施
Emricasan 5mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.
干预措施: Methacetin Breath Test (Combination Product)
Emricasan 5mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (5 mg) twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.
干预措施: Emricasan (Drug)
Emricasan 25mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.
干预措施: Methacetin Breath Test (Combination Product)
Emricasan 25mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (25 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.
干预措施: Emricasan (Drug)
Emricasan 50mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.
干预措施: Methacetin Breath Test (Combination Product)
Emricasan 50mg
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with emricasan (50 mg) twice a day. The MBT will be performed at screening, at week 24/ week 48/ at early termination.
干预措施: Emricasan (Drug)
Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.
干预措施: Methacetin Breath Test (Combination Product)
Placebo
Subjects with Non-alcoholic Steatohepatitis (NASH) Cirrhosis and Severe Portal Hypertension will be administered orally with a matching placebo twice a day. The MBT will be performed at screening, at week 24/week 48/at early termination.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Number of Subjects With Matched Clinically Significant Portal Hypertension Based on Hepatic Venous Pressure Gradient (HVPG) and Methacetin Breath Test (MBT)
时间窗: 1 hour for MBT related to assessment of this diagnostic primary outcome assesses during screening
Binary diagnosis of clinically significant portal hypertension (CSPH) as determined by HVPG, defined as HVPG ≥ 10mmHg and by the MBT derived from an algorithm developed under other Exalenz clinical studies
次要结局
- Number of Matched Subjects With Significant Portal Hypertension (Defined as HVPG>=12mmHg) Based on HVPG and MBT(1 hour for MBT for assessment of this diagnostic secondary outcome assessed during screening)