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

Sponsor

Suzhou Ribo Life Science Co. Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05017116

Collaborator

(none)

Enrollment

Location

Arms

32.7

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b	Drug: RBD1016 Drug: Placebo Drug: Entecavir	Phase 1

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

Anticipated Enrollment :

54 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 9, 2021

Anticipated Primary Completion Date :

Jun 22, 2023

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

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: RBD1016 subcutaneous injection Other Names: RBD1016 injection Drug: Placebo subcutaneous 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: RBD1016 subcutaneous injection Other Names: RBD1016 injection Drug: Placebo subcutaneous injection Drug: Entecavir Take orally.

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: RBD1016

subcutaneous injection

Other Names:

RBD1016 injection

Drug: Placebo

subcutaneous 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: RBD1016

subcutaneous injection

Other Names:

RBD1016 injection

Drug: Placebo

subcutaneous injection

Drug: Entecavir

Take orally.

Outcome Measures

Primary Outcome Measures

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

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 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 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 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 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 HBV RNA dynamic changes from baseline to Week 24 (Part A). [up to 24 weeks]
PCR will be used to detect HBV RNA.
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 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 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 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 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 t1/2 (Part A). [up to 85 days]
Half-Life (t1/2) 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 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 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 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 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 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 DNA dynamic changes from baseline to Week 24 (Part B). [up to 24 weeks]
PCR will be used to detect HBV DNA.
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 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 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.
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-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 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 t1/2 (Part B). [up to 113 days]
Half-Life (t1/2) 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 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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.