NCT03394924已完成2 期
A Phase 2 Dose Ranging, Randomized, Double Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of EDP-305 in Subjects With Primary Biliary Cholangitis (PBC) With or Without an Inadequate Response to Ursodeoxycholic Acid (UDCA)
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
- 68
- 试验地点
- 86
- 主要终点
- Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline
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 primary biliary cholangitis
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 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 a diagnosis of PBC by at least two of the following criteria:
- •History of ALP above ULN for at least six months
- •Positive Anti-Mitochondrial Antibodies (AMA) titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies)
- •For subjects with no documented liver biopsy performed within 2 years, subjects must undergo a transient elastography (Fibroscan) showing liver stiffness < 14.0 kPA
- •Must be on a stable dose of UDCA12-20 mg/kg/day for at least 6 months prior to Screening or intolerant of UDCA in the opinion of the Investigator (no UDCA for at least 12 weeks prior to Screening)
- •Alkaline Phosphatase (ALP) ≥ 1.67 × ULN and/or total bilirubin >ULN but < 2×ULN (<2.4 mg/dL)
- •Subjects must have Screening laboratory values for Hepatitis B surface antigen (HBsAg), anti-HCV antibodies and HCV RNA negative and Human Immunodeficiency Virus (HIV) 1 and 2 antibodies (Ab) as seronegative. Note: subjects previously infected by chronic hepatitis C and treated with direct acting antivirals (DAAs) with sustained virologic response (SVR) for at least 3 years will be allowed.
- •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-
- •All male participants who have not had a vasectomy must use effective contraception from Day -1 to 90 days after their last dose of study drug.
- •Male subjects must agree to refrain from sperm donation from the date of Screening until 90 days after their last dose of study drug
- •Screening body mass index (BMI) of ≥18 kg/m2
- •Subject must be willing and able to adhere to the assessments, visit schedule, prohibitions and restrictions, as described in this protocol
排除标准
- •Laboratory Screening Results:
- •AST >5 x ULN
- •ALT >5 x ULN
- •Patients with Gilbert's syndrome will not be allowed due to interpretability of bilirubin levels
- •Total white blood cells (WBC) <3000 cells/mm3
- •Absolute neutrophil count (ANC) <1500 cells/mm3
- •Platelet count <140,000/mm3
- •Prothrombin time (international normalized ratio, INR) >1.2
- •Serum creatinine >2 mg/dL or creatinine clearance <60 mL/min (based on Cockroft-Gault Method)
- •Suspected to have relevant nonalcoholic fatty liver disease (NAFLD) as based on the judgment of the Investigator at Screening
- •Use of immunosuppressants known to have an effect on the liver of patients with PBC (eg, colchicine, methotrexate, azathioprine, or systemic steroids) in the three months preceding screening
- •Current use of fibrates, including fenofibrates. Note: Subjects who discontinued fibrates for at least 3 months before Screening can participate
- •Use of an experimental treatment for PBC within the past 6 months
- •Co-existing liver or biliary diseases, such as primary sclerosing cholangitis, choledocholithiasis, acute or chronic hepatitis, autoimmune hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis (NASH), acute infection of bile duct system or gall bladder, history of gastrointestinal bleeding (secondary to portal hypertension), cirrhosis, cholangiocarcinoma diagnosed or suspected liver cancers
- •Cirrhosis with or without complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma
- •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)
- •Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease)
- •Use of a new statin regimen from Screening and throughout study duration. NOTE: Subjects on a stable dose of statins for at least 3 months prior to Screening are allowed. No dose modification during the study will be allowed.
- •Use of immunosuppressants (eg, systemic corticosteroids) for more than 2 consecutive weeks in duration within 1 year prior to Screening.
研究组 & 干预措施
EDP-305 1 mg
Experimental
Subjects will take 2 tablets once a day orally for 12 weeks
干预措施: EDP-305 1 mg (Drug)
EDP-305 2.5 mg
Experimental
Subjects will take 2 tablets once a day orally for 12 weeks
干预措施: EDP-305 2.5 mg (Drug)
Placebo
Placebo Comparator
Subjects will take two tablets once a day orally for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With At Least a 20% Reduction in Alkaline Phosphatase (ALP) or Normalization of ALP at Week 12 Compared to Baseline
时间窗: Baseline and Week 12
Percent change was calculated as \[(ALP at Week 12 - ALP at Baseline)/ALP at Baseline\] \*100. The participant was considered to have successfully achieved a 20% reduction in ALP if the result was ≤-20. The participant was considered to have successfully achieved ALP normalization if ALP was abnormal at Baseline and normal at Week 12.
次要结局
- Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: AST to Platelet Ratio Index (APRI) Score(Baseline and Week 12)
- Change From Baseline to Week 12 in Fibrinogen and C Reactive Protein (CRP) Levels(Baseline and Week 12)
- Change From Baseline to Week 12 in Interleukin (IL) and Tumor Necrosis Factor (TNF) Levels(Baseline and Week 12)
- Change From Baseline to Week 12 in Haptoglobin and Alpha2 Macroglobulin Levels(Baseline and Week 12)
- Change From Baseline to Week 12 in Triglycerides (TG), Total Cholesterol (TC), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C)(Baseline and Week 12)
- Change From Baseline to Week 12 in Total, Conjugated and Unconjugated Bilirubin(Baseline and Week 12)
- Percentage of Participants With a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period(Up to approximately Week 12)
- Percentage of Participants With a Treatment-Emergent Serious Adverse Event (SAE) During On-Treatment Period(Up to approximately Week 12)
- Percentage of Participants Who Stopped Study Treatment Due to a Treatment-Emergent Adverse Event (TEAE) During On-Treatment Period(Up to approximately Week 12)
- Change From Baseline to Week 12 in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT)(Baseline and Week 12)
- Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Fibrosis-4 (FIB-4) Score(Baseline and Week 12)
- Change From Baseline to Week 12 in Noninvasive Liver Fibrosis Markers: Enhanced Liver Fibrosis (ELF) Panel and N-terminal Type III Collagen Propeptide (PRO C3)(Baseline and Week 12)
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EDP-305 and Its Metabolites(Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose)
- Change From Baseline to Week 12 in Domain and Total Scores on the 5D-Itch Scale(Baseline and Week 12)
- Change From Baseline to Week 12 in Visual Analog Score (VAS) for Itching(Baseline to Week 12)
- Change From Baseline to Week 12 in Domain Scores on the Primary Biliary Cholangitis-40 (PBC-40) Quality of Life (QoL) Assessment(Baseline and Week 12)
- Maximum Plasma Concentration (Cmax) of EDP-305 and Its Metabolites(Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose)
- Time to Maximum Plasma Concentration (Tmax) of EDP-305 and Its Metabolites(Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose)
- Percentage Change From Baseline to Week 12 in Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA) Concentrations(Baseline and Week 12)
- Percentage Change From Baseline to Week 12 in AUC0-8 and AUC2-8 of Fibroblast Growth Factor 19 (FGF19), 7α-OH-4-cholesten-3-one (C4) and Bile Acid (BA)(Day 1 and Week 12: Pre-dose and 2, 6 and 8 hours post-dose)
研究者
研究点 (86)
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