A Phase 2a, Randomized, Double-blind, Placebo-controlled Study of Oral FXR Modulator EYP001a Combined With Nucleos(t)Ide Analogues (NA) in Virologically Suppressed Chronic Hepatitis B Patients to Improve Functional Cure Rates
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Enyo Pharma
- 入组人数
- 26
- 试验地点
- 18
- 主要终点
- HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment
研究概览
简要总结
This is a prospective, multi-centre, randomized, double-blind, placebo-controlled, Phase 2a experimental study of oral FXR modulator EYP001a/placebo combined with NAs in virologically suppressed CHB patients to improve functional cure rates.
详细描述
A total of 49 eligible patients will be enrolled and randomized at approximately 14 study sites. Patients will be randomized prior to study drug (EYP001a or placebo and NA) administration on Day 1 in the ratio of 3:1 into 2 arms:
- Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)
- Control Arm: Placebo + NA daily (12 patients)
The maximum total engagement duration for eligible patients in this study is up to 370 days: 90 days screening, 112 days (16 weeks) treatment period and 168 days (24 weeks) follow-up.
Patients enrolled in the study will be assessed as outpatients. Patient screening will occur no more than 90 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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Triple blind
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
- •Are on stable NA therapy at least 12 months from the screening date (ETV or TDF)
- •Has virally suppressed CHB:
- •HBV DNA <LLOQ and serum HBsAg >100 IU/mL
- •Has liver imaging to screen for hepatocellular carcinoma or concomitant pancreaticobiliary disease either in the prior 6 months or at screening.
- •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 contract research organization (CRO), vendor, or Sponsor involved with this study.
- •Has known hepatocellular carcinoma or pancreaticobiliary disease.
- •Neutropenia (defined by two confirmed values within screening period of <1500/μL).
- •Has Gilbert syndrome.
- •Shows evidence of worsening liver function, defined as either a confirmed (two assessments at least 3 days apart) increase >2 ULN ALT or AST or an increase of >1.5 × first assessed 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 F3 stage with a vibration controlled transient elastography (VCTE). Patients with normal baseline ALT and VCTE >8.8 kPa are excluded. Patients with baseline ALT >ULN (but <2ULN per EC5) and who have VCTE >10.5 kPa at baseline are excluded
- •Has known history of alcohol abuse or daily heavy alcohol consumption
- •Has clinically relevant immunosuppression, including, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
- •Has used anti-HBV medications other than NAs within 90 days prior to screening.
- •Has any of the following exclusionary laboratory results at screening:
- •Estimated glomerular filtration rate <60 mL/min/1.73 m2 (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
Experimental Arm
Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)
干预措施: EYP001a (Drug)
Experimental Arm
Experimental Arm: EYP001a Dose A QD + NA daily (37 patients)
干预措施: Nucleotide analogue (Entecavir or Tenofovir Disoproxil) (Drug)
Control Arm
Control Arm: Placebo + NA daily (12 patients)
干预措施: Placebo (Drug)
Control Arm
Control Arm: Placebo + NA daily (12 patients)
干预措施: Nucleotide analogue (Entecavir or Tenofovir Disoproxil) (Drug)
结局指标
主要结局
HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment
时间窗: LS mean at week 16 (Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, and Week 16)
Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment
次要结局
- Virologic Failure Rate(40 weeks)