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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects who voluntarily participate in this clinical trial, are able to correctly understand and have signed the informed consent in writing;
- •Male or female volunteer aged 18-55 years (inclusive);
- •Body Mass Index (BMI) of 18-30 kg/m2 (inclusive);
- •Subjects with chronic HBV infection, including immunotolerant subjects, treatment naïve subjects and treated subjects.
- •Ability to cooperate with study staff and comply with the study requirements and follow the protocol-specified procedures.
Exclusion Criteria
- •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;
- •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.);
- •Transient elastography at screening revealing FibroScan value ≥ 9 kPa or liver biopsy evidencing hepatic fibrosis within 24 months;
- •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;
- •12-lead ECG abnormalities with clinical significance;
- •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);
- •Other factors that in the investigator's opinion would make it inappropriate for the subject to participate in the study.
Arms & Interventions
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Intervention: Placebo (Drug)
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Intervention: RBD1016 (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Intervention: RBD1016 (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Intervention: Placebo (Drug)
Part A，single dose group
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Intervention: Entecavir (Drug)
Part B, multiple dose group
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Intervention: Entecavir (Drug)
Outcomes
Primary Outcomes
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
Time Frame: up to 28 days
All reported AE terms will be coded using Medical Dictionary for Drug Regulatory Affairs (MedDRA).AEs and SAEs occurred throughout the course of the study will be evaluated and graded based on NCI-CTCAE V5.0.
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)
Time Frame: up to 28 days
All reported AE terms will be coded using Medical Dictionary for Drug Regulatory Affairs (MedDRA).AEs and SAEs occurred throughout the course of the study will be evaluated and graded based on NCI-CTCAE V5.0.
Secondary Outcomes
- To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-inf (Part A).(up to 85 days)
- To characterize the pharmacokinetic parameter Vd (Part A).(up to 85 days)
- To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter t1/2 (Part B).(up to 113 days)
- To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Tmax (Part A).(up to 85 days)
- To characterize the pharmacokinetic parameter CL/F (Part A)(up to 85 days)
- To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Tmax (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter AUC0-inf (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter Vd (Part B).(up to 113 days)
- To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter t1/2 (Part A).(up to 85 days)
- To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-t (Part A).(up to 85 days)
- To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of B cell dynamic changes from baseline to Week 24 (Part A).(up to 24 weeks)
- To characterize the pharmacokinetic parameter Cmax (Part A).(up to 85 days)
- To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To draw the figure of B cell dynamic changes from baseline to Week 24 (Part B).(up to 24 weeks)
- To characterize the pharmacokinetic parameter AUC0-t (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter CL/F (Part B).(up to 113 days)
- To characterize the pharmacokinetic parameter Cmax (Part B).(up to 113 days)