A Single and Repeated Dose Escalation of RBD1016 in Subjects With Chronic Hepatitis B Virus (HBV) Infection

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Placebo; Drug: RBD1016; Drug: Entecavir

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hong Kong, China
    • The University of Hong Kong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A，single dose group; Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.	Drug: Placebo; subcutaneous injection; Drug: RBD1016; subcutaneous injection; Other Names: RBD1016 injection; Drug: Entecavir; Take orally.
Experimental: 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.	Drug: Placebo; subcutaneous injection; Drug: RBD1016; subcutaneous injection; Other Names: RBD1016 injection; Drug: Entecavir; Take orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)	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.	up to 28 days
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)	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.	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B surface antigen (HBsAg).	up to 24 weeks
To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B surface antibody (HBsAb).	up to 24 weeks
To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B e antigen (HBeAg).	up to 24 weeks
To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B e antibody (HBeAb).	up to 24 weeks
To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B core antibody (HBcAb).	up to 24 weeks
To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part A).	Electro chmiluminescence method will be used to detect hepatitis B core-related antigen (HBcrAg).	up to 24 weeks
To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).	PCR will be used to detect HBV DNA.	up to 24 weeks
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).	PCR will be used to detect HBV RNA.	up to 24 weeks
To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part A).	Flow Cytometry will be used to detect peripheral blood T lymphocyte subsets.	up to 24 weeks
To draw the figure of B cell dynamic changes from baseline to Week 24 (Part A).	Flow Cytometry will be used to detect B cell count.	up to 24 weeks
To characterize the pharmacokinetic parameter Cmax (Part A).	PCR will be ued to detect Maximum concentration (Cmax) and PhoenixWinNonlin software (V8.0 or higher) will be used to calculate the PK parameters.	up to 85 days
To characterize the pharmacokinetic parameter Tmax (Part A).	Time to maximum concentration (Tmax) will be calculated by PhoenixWinNonlin software (V8.0 or higher) will be used to calculate the PK parameter.	up to 85 days
To characterize the pharmacokinetic parameter AUC0-t (Part A).	Area under the concentration-time curve from 0 to the collection time t (AUC0-t) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 85 days
To characterize the pharmacokinetic parameter AUC0-inf (Part A).	Area under the concentration-time curve from 0 to infinity (AUC0-inf) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 85 days
To characterize the pharmacokinetic parameter t1/2 (Part A).	Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 85 days
To characterize the pharmacokinetic parameter Vd (Part A).	Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 85 days
To characterize the pharmacokinetic parameter CL/F (Part A)	Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 85 days
To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B surface antigen (HBsAg).	up to 24 weeks
To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B surface antibody (HBsAb).	up to 24 weeks
To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B e antigen (HBeAg).	up to 24 weeks
To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B e antibody (HBeAb).	up to 24 weeks
To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B core antibody (HBcAb).	up to 24 weeks
To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part B).	Electro chmiluminescence method will be used to detect hepatitis B core-related antigen (HBcrAg).	up to 24 weeks
To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part B).	PCR will be used to detect HBV DNA.	up to 24 weeks
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).	PCR will be used to detect HBV RNA.	up to 24 weeks
To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part B).	Flow Cytometry will be used to detect peripheral blood T lymphocyte subsets.	up to 24 weeks
To draw the figure of B cell dynamic changes from baseline to Week 24 (Part B).	Flow Cytometry will be used to detect B cell count.	up to 24 weeks
To characterize the pharmacokinetic parameter Cmax (Part B).	PCR will be ued to detect Maximum concentration (Cmax) and PhoenixWinNonlin software (V8.0 or higher) will be used to calculate the PK parameters.	up to 113 days
To characterize the pharmacokinetic parameter Tmax (Part B).	Time to maximum concentration (Tmax) will be calculated by PhoenixWinNonlin software (V8.0 or higher) will be used to calculate the PK parameter.	up to 113 days
To characterize the pharmacokinetic parameter AUC0-t (Part B).	Area under the concentration-time curve from 0 to the collection time t (AUC0-t) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 113 days
To characterize the pharmacokinetic parameter AUC0-inf (Part B).	Area under the concentration-time curve from 0 to infinity (AUC0-inf) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 113 days
To characterize the pharmacokinetic parameter t1/2 (Part B).	Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 113 days
To characterize the pharmacokinetic parameter Vd (Part B).	Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 113 days
To characterize the pharmacokinetic parameter CL/F (Part B).	Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher).	up to 113 days

Collaborators and Investigators

• Sponsor: Suzhou Ribo Life Science Co. Ltd.
• Investigators: Principal Investigator: Walter Seto, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Actual): October 25, 2023
• Study Completion (Actual): October 25, 2023

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 30, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: CHB; chronic hepatitis B infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: RBHB1103-HK

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No