Clinical trial NCT05017116: A Single and Repeated Dose Escalation of RBD1016 in Subjects with Chronic Hepatitis B Virus (HBV) Infection
Official title: A Single and Repeated Dose Escalation, Phase I Clinical Study to Evaluate the Safety, Pharmacokinetics and Preliminary Pharmacodynamics of RBD1016 in Subjects with Chronic Hepatitis B Virus (HBV) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis B
Keywords: CHB
chronic hepatitis B infection
Lead sponsor: Suzhou Ribo Life Science Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, single (Part A) and repeated dose (Part B) escalation, phase I clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary pharmacodynamics (PD) of RBD1016 in subjects with chronic HBV infection.

Detailed description: The study consists of two parts. Part A is the single dose escalation study where subjects with chronic HBV infection will be assigned to receive single dose of RBD1016 or placebo . Part B is the multiple dose escalation study where subjects with chronic HBV infection will be assigned to receive two doses of RBD1016 or placebo.

Eligibility criteria: Inclusion Criteria:

1. Subjects who voluntarily participate in this clinical trial, are able to correctly understand and have signed the informed consent in writing;
2. Male or female volunteer aged 18-55 years (inclusive);
3. Body Mass Index (BMI) of 18-30 kg/m2 (inclusive);
4. Subjects with chronic HBV infection, including immunotolerant subjects, treatment naïve subjects and treated subjects.
5. Ability to cooperate with study staff and comply with the study requirements and follow the protocol-specified procedures.

Exclusion Criteria:

1. Subjects with liver diseases other than hepatitis B, including hepatitis C, hemochromatosis, primary sclerosing cholangitis; alcoholic, drug-related or autoimmune liver diseases; primary liver cancer and indeterminate nodules on liver imaging test;
2. A history or manifestations of liver decompensation (e.g. Child-Pugh Class B or C, or ascites, gastrointestinal bleeding, hepatic encephalopathy or spontaneous bacterial peritonitis, etc.);
3. Transient elastography at screening revealing FibroScan value ≥ 9 kPa or liver biopsy evidencing hepatic fibrosis within 24 months;
4. The following laboratory findings: total serum bilirubin\> 2×ULN; serum alpha-fetoprotein\>50μg/L; serum albumin \<3.5g/dL; international normalized ratio (INR)\> 1.25; serum creatinine \> 1.5×ULN; any laboratory outliers of clinical significance that in the investigator's opinion may interfere with the interpretation of efficacy or safety data;
5. 12-lead ECG abnormalities with clinical significance;
6. Pregnant or lactating women or women of child-bearing potential who are unwilling to take effective contraception throughout the course of the study (refer to Appendix 3 for details);
7. Other factors that in the investigator's opinion would make it inappropriate for the subject to participate in the study.

Primary outcomes:
measure: Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
timeFrame: up to 28 days
measure: Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)
timeFrame: up to 28 days
Secondary outcomes:
measure: To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To draw the figure of B cell dynamic changes from baseline to Week 24 (Part A).
timeFrame: up to 24 weeks
measure: To characterize the pharmacokinetic parameter Cmax (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter Tmax (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter AUC0-t (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter AUC0-inf (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter t1/2 (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter Vd (Part A).
timeFrame: up to 85 days
measure: To characterize the pharmacokinetic parameter CL/F (Part A)
timeFrame: up to 85 days
measure: To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To draw the figure of B cell dynamic changes from baseline to Week 24 (Part B).
timeFrame: up to 24 weeks
measure: To characterize the pharmacokinetic parameter Cmax (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter Tmax (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter AUC0-t (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter AUC0-inf (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter t1/2 (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter Vd (Part B).
timeFrame: up to 113 days
measure: To characterize the pharmacokinetic parameter CL/F (Part B).
timeFrame: up to 113 days
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Walter Seto
role: PRINCIPAL_INVESTIGATOR
References: