A Phase 2a Open-label Study of the Oral Farnesoid X Receptor (FXR) Modulator EYP001a to Assess Its Safety and Anti-viral Effect in Chronic Hepatitis B (CHB) Patients in Combination With Pegylated Interferon alpha2a (Peg-IFN) Alone and With Entecavir (ETV)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Enyo Pharma
- 入组人数
- 20
- 试验地点
- 6
- 主要终点
- Measurement of HBsAg decline
研究概览
简要总结
This is a multi centre, two parallel arm, randomized, open-label, Phase 2a experimental study of oral Farnesoid X Receptor (FXR) modulator EYP001a to assess its safety and anti-viral effect when administered to non-treated (treatment naive or off treatment) chronic Hepatitis B (CHB) patients in combination with entecavir (ETV) and pegylated interferon alpha2a (peg-IFN). An experimental treatment period of 16 weeks will be followed by a 24 week maintenance period with ETV standard of care (SoC).
详细描述
In total 30 eligible patients will be enrolled and randomized at approximately 7 study sites.
Patients will be randomized prior to study drug (EYP001a, ETV and peg-IFN) administration on Day 1 in the ratio of 1:1 into 2 treatment arms:
- Arm 1: EYP001a QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
- Arm 2: EYP001a QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW (± 3 days) (15 patients)
Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 37 days prior to the Day 1 visit. Eligible patients will undergo further assessments on Day 1 to qualify for study drug administration on Day 1.
The visits during the study are planned as below:
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has given voluntary written informed consent before performance of any study related procedure.
- •Are treatment naive or without HBV treatment for at least 60 days or 5 times the elimination half-life, whichever is longer.
- •Patient has CHB:
- •HBV DNA ≥ 20,000 IU/mL for HBeAg positive and ≥2'000 for HBeAg negative and
- •HBsAg ≥ 2.5 log10 IU/mL.
- •Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
- •Patient is not of childbearing potential or, if of childbearing potential, is not pregnant as confirmed by a negative serum human chorionic gonadotropin test at screening and is not planning a pregnancy during the course of the study.
排除标准
- •Is an employee of a clinical research organization, vendor, or Sponsor involved with this study.
- •Has known hepatocellular carcinoma or pancreaticobiliary disease.
- •Neutropenia (defined by two confirmed values during Screening period of < 1500/μL).
- •Has Gilbert syndrome.
- •Shows evidence of worsening liver tests, defined as either a confirmed (2 assessments at least 3 days apart) increase > 2 ULN ALT or AST or an increase of > 1.5 × baseline value of TBL or associated with clinical signs or symptoms of liver impairment.
- •Has known or suspected non-CHB liver disease
- •History of cirrhosis or liver decompensation, including ascites, hepatic encephalopathy, or presence of oesophageal varices.
- •Probable or possible F4 stage with a vibration controlled transient elastography (VCTE) > 11.7 kPa leads to exclusion
- •Has known history of alcohol abuse or daily heavy alcohol consumption
- •Has any of the following exclusionary laboratory results at screening:
- •ALT > 2 × ULN, AST > 2 × ULN
- •INR > 1.2 × ULN, (normal range is 0.8 to 1.2)
- •Platelet count < 100 G/L
- •Estimated glomerular filtration rate < 50 mL/min/1.73m2 (the Modification of Diet in Renal Disease formula)
- •Thyroid-stimulating hormone > 1.5 × ULN or abnormal free triiodothyronine or free thyroxine.
研究组 & 干预措施
Arm 1
EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
干预措施: EYP001a (Drug)
Arm 1
EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
干预措施: Entecavir (Drug)
Arm 1
EYP001a Dose A QD + ETV 0.5 mg QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
干预措施: Pegylated interferon alpha2a (Drug)
Arm 2
EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
干预措施: EYP001a (Drug)
Arm 2
EYP001a Dose A QD + peg-IFN dosed per body surface area (180 µg, 135 µg or 90 µg) QW
干预措施: Pegylated interferon alpha2a (Drug)
结局指标
主要结局
Measurement of HBsAg decline
时间窗: 16 weeks
Measurement of HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment period
Number of Treatment-emergent adverse events
时间窗: 16 weeks
Number of Treatment-emergent adverse events including serious adverse events
次要结局
- Measurement of HBV-DNA decline(40 weeks)
- Measurement of HBcrAg decline(40 weeks)
- Measurement of HBV-pgRNA decline(40 weeks)
- Concentration of C4 - Pharmacodynamic biomarker(40 weeks)
- Measurement of HBsAg decline(40 weeks)
- Concentration of EYP001a - Pharmacokinetic(20 weeks)
- Concentration of FGF19 - Pharmacodynamic biomarker(40 weeks)
- Concentration of Bile Acids - Pharmacodynamic biomarker(40 weeks)