A Phase 2a, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of RBD1016 in Participants With Chronic Hepatitis D Virus Infection, Including a Randomised, Single Blinded, Placebo-controlled Exploratory Part
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Mean change (log10 value) vs. baseline in HDV RNA levels in plasma at end of trial (Week 60).
研究概览
简要总结
The goal of this clinical trial is to learn if drug RBD1016 works to treat chronic hepatitis D virus infection in adults. It will also learn about the safety of drug RBD1016. The main questions it aims to answer are:
Does drug RBD106 reduce the HDV RNA levels? What medical problems may participants experience when taking drug RBD1016? Researchers will compare drug RBD1016 to a placebo to see if drug RBD1016 works to treat chronic hepatitis D.
Participants will:
Receive drug RBD1016 or a placebo several times throughout the trial. Visit the clinic once every 4-6 weeks for checkups and tests.
详细描述
This is a multicentre, randomised, partly blinded, placebo-controlled clinical trial to evaluate the efficacy, safety and pharmacokinetics (PK) of RBD1016 subcutaneous injections in participants with chronic HDV infection.
First part of the trial: There will be 2 treatment groups - an active group (n=10) and a deferred active group (n=5), with participants allocated randomly. In the active group, participants will receive RBD1016. In the deferred active group, participants will receive 4 doses of placebo followed by deferred treatment with doses of RBD1016.
Both groups will be on a stable nucleoside analogue (NA) treatment course during the trial . All participants will be blinded to the trial treatment for the 16 weeks after the first dose. Then, investigators and other clinic staff will be unblinded, i.e., they will know which treatment the participants receive at all times.
Open-label extension part (site 01 only): continued IMP-treatment with additionally 3 doses of IMP administered 12 weeks apart. This part of the trial is conducted to collect long-term safety data and further exploratory efficacy measures. Only participants who may benefit from continued treatment in the ,trial, according to the judgement of the investigator, will be eligible for the open-label extension part of the trial.
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
盲法说明
First part of the trial: All participants will be blinded to the trial treatment for the first 16 weeks after the first dose. Then, investigators and other clinic staff will be unblinded, i.e., they will know which treatment the participants receive at all times.
Open-label extension part: additionally 3 doses of active IMP administered 12 weeks apart (site 01 only).
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
- •Willing and able to give written informed consent for participation in the trial.
- •Male or female participant aged 18 to 65 years, inclusive.
- •Body mass index (BMI) ≥ 18 and ≤ 35 kg/m2 at the time of the screening visit.
- •Documented evidence of HDV infection in medical history, i.e., HDV antibodies (HDVAb) and/or HDV RNA positive test results within at least 6 months prior to screening.
- •Documented evidence of HBV infection in medical history, i.e., HBsAg and/or HBV DNA positive test results within at least 6 months prior to screening.
- •Documented absence of liver cirrhosis, defined as an LSM ≥ 10 kPa measured on FibroScan® elastography at screening.
排除标准
- •Laboratory results at screening as follows, or any clinically significant laboratory parameter outliers that may interfere with the evaluation of efficacy and/or safety in the trial, at the discretion of the Investigator:
- •α-fetoprotein (AFP) > 50 µg/L.
- •Albumin concentration < 3.0 g/dL.
- •International normalized ratio (INR) > 1.
- •Platelet count < 90 × 109/L.
- •Direct bilirubin > 2 × ULN, Gilbert syndrome excluded.
- •Creatinine concentration > 1.5 × ULN.
- •Creatinine clearance < 60 mL/min, according to the Cockcroft-Gault equation.
- •Positive result at screening for hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) and/or prior diagnosis of syphilis, acute hepatitis A and/or acute hepatitis E.
- •Prior diagnosis of other liver diseases of non-HBV or non-HDV aetiology, including autoimmune liver disease (e.g., autoimmune hepatitis, primary biliary cholangitis or primary sclerosing cholangitis), inherited metabolic liver disease (e.g., haemochromatosis, Wilson's disease, familial intrahepatic cholestasis), drug-induced liver disease and/or non alcoholic steatohepatitis (NASH) assessed as moderate or above, at the discretion of the Investigator.
- •Prior or current diagnosis of liver cirrhosis.
- •History of or active hepatic decompensation, e.g., ascites, variceal bleeding or hepatic encephalopathy, at the discretion of the Investigator.
- •History of organ transplantation, previous or concurrent HCC or imaging finding suggesting malignant liver lesions, at the discretion of the Investigator.
- •Signs of liver malignancy in abdominal ultrasound at screening.
研究组 & 干预措施
Active group
Participants will receive RBD1016 (subcutaneous injections).
干预措施: RBD1016 (Drug)
Deferred active group
Participants will receive 4 doses of placebo (subcutaneous injections) followed by RBD1016 (subcutaneous injections).
干预措施: RBD1016 (Drug)
Deferred active group
Participants will receive 4 doses of placebo (subcutaneous injections) followed by RBD1016 (subcutaneous injections).
干预措施: Placebo (Drug)
结局指标
主要结局
Mean change (log10 value) vs. baseline in HDV RNA levels in plasma at end of trial (Week 60).
时间窗: 60 weeks
次要结局
- Frequency, intensity and seriousness of reported AEs, SAEs and AEs of special interest (AESIs) during the trial.(60 weeks)
- Mean change (log10 value) in HBsAg levels vs. baseline, at end of trial (Week 60).(60 weeks)
- Proportion of participants with positive immunogenicity, measured as plasma concentrations of anti-drug antibodies (ADAs), at each evaluation time point up to end of the study at week 60.(60 weeks)
- Mean maximum change (log10 value) in HDV RNA levels in plasma vs. baseline, at any timepoint during the study, and up to the end of study at Week 60.(Up to 60 weeks)
- Mean maximum change (log10 value) in HBsAg levels vs. baseline, at any timepoint during the study, and up to end of study at Week 60.(Up to 60 weeks)
- For participants with HBsAg levels more than100 IU/mL at baseline: Proportion of participants with HBsAg levels ≤ 10 IU/mL at end of trial (Week 60).(60 weeks)
- Proportion of participants with undetectable HDV RNA (i.e., less than the limit of detection), or ≥ 2 log10 decrease in HDV RNA and alanine transaminase (ALT) normalisation, at end of trial (Week 60).(60 weeks)
- Proportion of participants with undetectable HDV RNA (i.e., less than the limit of detection) or ≥ 2 log10 decrease in HDV RNA at end of trial (Week 60).(60 weeks)
- Plasma concentrations of RBD1016.(60 weeks)