NCT03421431已完成2 期
A Phase 2 Dose Ranging, Randomized, Double Blind, and Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Non-Alcoholic Steatohepatitis (NASH)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 134
- 试验地点
- 81
- 主要终点
- Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12
研究概览
简要总结
A randomized, double-blind study to assess the safety, tolerability, PK and efficacy of EDP-305 in subjects with Non-Alcoholic Steatohepatitis
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •An informed consent document must be signed and dated by the subject
- •Male and female subjects of any ethnic origin between the ages of 18 and 75 years, inclusive
- •Male or female with presence of NASH by:
- •Histologic evidence on a historical liver biopsy within 24 months of Screening consistent with NASH with fibrosis (no cirrhosis), and elevated ALT at Screening AND Screening MRI PDFF with >8 % steatosis OR
- •Phenotypic diagnosis of NASH based on elevated ALT and diagnosis of T2DM or pre-diabetes AND Screening MRI PDFF with >8 % steatosis
- •Body mass index (BMI) >25 kg/m2; for Asian-Americans, BMI >23 kg/m2
- •Female subjects of childbearing potential must agree to use two effective methods of contraception from the date of Screening until 90 days after the last dose of EDP-
- •Subject must be willing and able to adhere to the assessments, visit schedules, prohibitions and restrictions, as described in this protocol
排除标准
- •Laboratory Screening Results:
- •Total bilirubin > ULN (normal range 0.2-1.2 mg/dL)
- •Total white blood cells (WBC) <3,000 cells/mm3
- •Absolute neutrophil count (ANC) <1,500 cells/mm3
- •Platelet count <140,000/mm3
- •Prothrombin time (international normalized ratio, INR) > 1.2
- •Creatine kinase above the upper limit of normal (ULN) except when in relation with intense exercise
- •Serum creatinine >2 mg/dL or creatinine clearance <60 ml/min (based on Cockroft Gault method)
- •Known history of alpha-1-antitrypsin deficiency
- •Use of an experimental treatment for NASH within the past 6 months
- •Use of immunosuppressant (eg, corticosteroids) for more than 2 weeks in duration within 1 year prior to Screening and during the course of the study
- •Use of experimental or unapproved drugs within a year of Screening
- •Any other condition(s) (including cardiovascular diseases) that would compromise the safety of the subject or compromise the quality of the clinical study, as judged by the Principal Investigator (PI)
- •Pregnant or nursing females
- •Recipients of liver or other organ transplantation or anticipated need for orthotropic organ transplantation in one year as determined by a Model for End-Stage Liver Disease (MELD) Score ≥ 15
- •Clinical suspicion of advanced liver disease or cirrhosis
- •Coexisting liver or biliary diseases, such as primary sclerosing cholangitis (PSC), choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis
- •Suspicion of cancer (eg, liver cancer) with the exception of basal cell carcinoma that has been resected
- •Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma, bilirubin > 2xULN
- •Hepatorenal syndrome (type I or II) or Screening serum creatinine > 2 mg/dL (178 μmol/L)
- •Prior variceal hemorrhage, uncontrolled encephalopathy, Child-Pugh Class A, B, and C, esophageal varices, or refractory ascites within the previous 6 months of Screening (defined as date informed consent signed)
- •Any condition possibly affecting drug absorption (eg, gastrectomy <3 years prior to Screening)
- •Subject has received an investigational agent or vaccine within 30 days, or a biological product within 3 months or 5 elimination half-lives (whichever is longer) prior to the planned intake of study drug. NOTE: Flu vaccine will be allowed upon Medical Monitor's approval
- •Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least three months prior to Screening are allowed. No dose modification during the study will be allowed.
- •Current use of fibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate
- •Clinically significant history of drug sensitivity or allergy, as determined by the PI
- •Uncontrolled diabetes mellitus (ie, HbA1c ≥9% or higher) 60 days prior to Day 1
- •Subjects with contraindications to MRI imaging, or not being able to have the MRI performed
研究组 & 干预措施
Placebo
Placebo Comparator
Subjects will take 2 tablets once a day orally for 12 weeks
干预措施: Placebo (Drug)
EDP-305 Dose 1
Experimental
Subjects will take 2 tablets once a day orally for 12 weeks
干预措施: EDP-305 Dose 1 (Drug)
EDP-305 Dose 2
Experimental
Subjects will take 2 tablets once a day orally for 12 weeks
干预措施: EDP-305 Dose 2 (Drug)
结局指标
主要结局
Mean Change From Baseline (Average) in Alanine Aminotransferase (ALT) at Week 12
时间窗: Baseline and Week 12
Blood samples were collected at specific timepoints for the laboratory evaluation to assess the ALT level. Baseline refers to the average of the screening and the Day 1 values; if either the screening or Day 1 values were missing, the non-missing value was used. Mean change was defined as the mean value at Week 12 minus the mean value at baseline.
次要结局
- Mean Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Apolipoproteins A1 (ApoA-1) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Apolipoproteins B (ApoB) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Fasting Blood Glucose at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Homeostasis Model Assessment (HOMA) Index for Nondiabetic Participants at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Fibroblast Growth Factor 19 (FGF19) by Nominal Timepoint (Intensive Pharmacodynamic [PD] Samples) at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12))
- Mean Change From Baseline in Aspartate Aminotransferase to Platelet Ratio Index (APRI) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Percentage of Fat in the Liver as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Triglycerides (TG) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Apolipoproteins C3 (ApoC3) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Fasting Insulin at Week 12(Baseline and Week 12)
- Cmax of EP-022571 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Tmax of EP-022571 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- AUC(Last) of EP-022571 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Cmax of EP-022572 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Tmax of EP-022572 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Mean Change From Baseline in Total Cholesterol at Week 12(Baseline and Week 12)
- Mean Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Adiponectin at Week 12(Baseline and Week 12)
- Mean Change From Baseline in HOMA Index for Diabetic Participants at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Glycated Hemoglobin (HbA1c) in Participants With T2DM at Week 12(Baseline and Week 12)
- Maximum Plasma Concentration (Cmax) of EDP-305 on Day 1 and Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Time to Reach Maximum Plasma Concentration (Tmax) of EDP-305 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Area Under the Plasma Concentration-Time Curve (AUC) From Time Zero to the Time of the Last Quantifiable Concentration (AUC[Last]) of EDP-305 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Tmax of EP-022679 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Mean Change From Baseline in FGF19 by Bin Timepoint (Sparse PD Samples) at Week 12(Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12))
- AUC(Last) of EP-022572 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Mean Change From Baseline in BA by Bin Timepoint (Sparse PD Samples) at Week 12(Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12))
- Cmax of EP-022679 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Mean Change From Baseline in 7a-Hydroxy-4-Cholestene-3-One (C4) by Nominal Timepoint (Intensive PD Samples) at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12))
- Mean Change From Baseline in C4 by Bin Timepoint (Sparse PD Samples) at Week 12(Predose and two samples postdose (first sample between 1 to 3 hours postdose and second sample 1 hour later than fist sample) on Day 1 and Day 84 (Week 12))
- Mean Change From Baseline in Bile Acid (BA) by Nominal Timepoint (Intensive PD Samples) at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and Day 84 (Week 12))
- AUC(Last) of EP-022679 on Day 1 and at Week 12(Predose and 2, 6, and 8 hours postdose on Day 1 and on Day 84 (Week 12))
- Mean Change From Baseline in Body Weight at Week 12(Baseline and Week 12)
- Mean Change From Baseline in Waist to Hip (WTH) Ratio at Week 12(Baseline and Week 12)
研究者
研究点 (81)
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