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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: RBD1016; Drug: Placebo; Drug: Entecavir

• Registration Number: NCT05017116
• Lead Sponsor: Suzhou Ribo Life Science Co. Ltd.

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 Timeline

• Study Start: 2021-08-09
• Study First Submitted: 2021-08-10
• Study First Submitted QC: 2021-08-18
• Study First Posted: 2021-08-23
• Status Verified: 2023-10
• Primary Completion: 2023-10-25
• Study Completion: 2023-10-25
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part B, multiple dose group	Placebo	Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Part A，single dose group	Placebo	Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Part B, multiple dose group	RBD1016	Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Part A，single dose group	RBD1016	Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Part A，single dose group	Entecavir	Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Part B, multiple dose group	Entecavir	Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.

Primary Outcome Measures

Name	Time	Method
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)	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)	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 Outcome Measures

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

Trial Locations

Locations (1)

The University of Hong Kong; 🇨🇳 Hong Kong, China