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

Suzhou Ribo Life Science Co. Ltd.40 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Chronic Hepatitis B

Interventions

RBD1016DRUG

subcutaneous injection

PlaceboDRUG

subcutaneous injection

EntecavirDRUG

Take orally.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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.

Locations (1)

The University of Hong Kong

Hong Kong, China

Outcomes

Primary Outcomes

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.

Time frame: up to 28 days

Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)

Time frame: up to 28 days

Secondary Outcomes

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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: up to 24 weeks

Data from ClinicalTrials.gov

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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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: up to 113 days