Back to resultsA Single and Repeated Dose Escalation of RBD1016 in Subjects With Chronic Hepatitis B Virus (HBV) Infection
Primary Purpose
Chronic Hepatitis b
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
RBD1016
Placebo
Entecavir
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis b focused on measuring CHB, chronic hepatitis B infection
Eligibility Criteria
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.
Sites / Locations
- The University of Hong KongRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part A，single dose group
Part B, multiple dose group
Arm Description
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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).
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).
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).
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).
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).
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).
To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).
PCR will be used to detect HBV DNA.
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).
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).
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).
Flow Cytometry will be used to detect B cell count.
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.
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.
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).
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).
To characterize the pharmacokinetic parameter t1/2 (Part A).
Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
To characterize the pharmacokinetic parameter Vd (Part A).
Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
To characterize the pharmacokinetic parameter CL/F (Part A)
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).
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).
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).
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).
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).
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).
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).
PCR will be used to detect HBV DNA.
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).
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).
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).
Flow Cytometry will be used to detect B cell count.
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.
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.
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).
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).
To characterize the pharmacokinetic parameter t1/2 (Part B).
Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
To characterize the pharmacokinetic parameter Vd (Part B).
Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
To characterize the pharmacokinetic parameter CL/F (Part B).
Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Full Information
NCT ID
NCT05017116
First Posted
August 10, 2021
Last Updated
April 24, 2022
Sponsor
Suzhou Ribo Life Science Co. Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05017116
Brief Title
A Single and Repeated Dose Escalation of RBD1016 in Subjects With Chronic Hepatitis B Virus (HBV) Infection
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 9, 2021 (Actual)
Primary Completion Date
June 22, 2023 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Suzhou Ribo Life Science Co. Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b
Keywords
CHB, chronic hepatitis B infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A，single dose group
Arm Type
Experimental
Arm Description
Subjects will receive single dose RBD1016/placebo on D1 combined with antiviral drugs during the study period.
Arm Title
Part B, multiple dose group
Arm Type
Experimental
Arm Description
Subjects will receive two doses of RBD1016/placebo on D1 and D29 combined with antiviral drugs during the study period.
Intervention Type
Drug
Intervention Name(s)
RBD1016
Other Intervention Name(s)
RBD1016 injection
Intervention Description
subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
Take orally.
Primary Outcome Measure Information:
Title
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after treatment (Part A)
Description
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
Title
Adverse events (AEs) and serious adverse events (SAEs) within 28 days after the last treatment(Part B)
Description
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
Secondary Outcome Measure Information:
Title
To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B surface antigen (HBsAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B surface antibody (HBsAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B e antigen (HBeAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B e antibody (HBeAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B core antibody (HBcAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part A).
Description
Electro chmiluminescence method will be used to detect hepatitis B core-related antigen (HBcrAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part A).
Description
PCR will be used to detect HBV DNA.
Time Frame
up to 24 weeks
Title
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part A).
Description
PCR will be used to detect HBV RNA.
Time Frame
up to 24 weeks
Title
To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part A).
Description
Flow Cytometry will be used to detect peripheral blood T lymphocyte subsets.
Time Frame
up to 24 weeks
Title
To draw the figure of B cell dynamic changes from baseline to Week 24 (Part A).
Description
Flow Cytometry will be used to detect B cell count.
Time Frame
up to 24 weeks
Title
To characterize the pharmacokinetic parameter Cmax (Part A).
Description
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
Title
To characterize the pharmacokinetic parameter Tmax (Part A).
Description
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
Title
To characterize the pharmacokinetic parameter AUC0-t (Part A).
Description
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
Title
To characterize the pharmacokinetic parameter AUC0-inf (Part A).
Description
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
Title
To characterize the pharmacokinetic parameter t1/2 (Part A).
Description
Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 85 days
Title
To characterize the pharmacokinetic parameter Vd (Part A).
Description
Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 85 days
Title
To characterize the pharmacokinetic parameter CL/F (Part A)
Description
Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 85 days
Title
To draw the figure of HBsAg dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B surface antigen (HBsAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBsAb dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B surface antibody (HBsAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBeAg dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B e antigen (HBeAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBeAb dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B e antibody (HBeAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBcAb dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B core antibody (HBcAb).
Time Frame
up to 24 weeks
Title
To draw the figure of HBcrAg dynamic changes from baseline to Week 24 (Part B).
Description
Electro chmiluminescence method will be used to detect hepatitis B core-related antigen (HBcrAg).
Time Frame
up to 24 weeks
Title
To draw the figure of HBV DNA dynamic changes from baseline to Week 24 (Part B).
Description
PCR will be used to detect HBV DNA.
Time Frame
up to 24 weeks
Title
To draw the figure of HBV RNA dynamic changes from baseline to Week 24 (Part B).
Description
PCR will be used to detect HBV RNA.
Time Frame
up to 24 weeks
Title
To draw the figure of peripheral blood T lymphocyte subsets dynamic changes from baseline to Week 24 (Part B).
Description
Flow Cytometry will be used to detect peripheral blood T lymphocyte subsets.
Time Frame
up to 24 weeks
Title
To draw the figure of B cell dynamic changes from baseline to Week 24 (Part B).
Description
Flow Cytometry will be used to detect B cell count.
Time Frame
up to 24 weeks
Title
To characterize the pharmacokinetic parameter Cmax (Part B).
Description
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
Title
To characterize the pharmacokinetic parameter Tmax (Part B).
Description
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
Title
To characterize the pharmacokinetic parameter AUC0-t (Part B).
Description
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
Title
To characterize the pharmacokinetic parameter AUC0-inf (Part B).
Description
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
Title
To characterize the pharmacokinetic parameter t1/2 (Part B).
Description
Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 113 days
Title
To characterize the pharmacokinetic parameter Vd (Part B).
Description
Apparent volume of distribution (Vd) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 113 days
Title
To characterize the pharmacokinetic parameter CL/F (Part B).
Description
Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher).
Time Frame
up to 113 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Walter Seto
Phone
+8522554086
Email
wkseto@hku.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Seto
Organizational Affiliation
The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Hong Kong
City
Hong Kong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Managing Director
Phone
+85222552547
Email
ctcentre@hku.hk
12. IPD Sharing Statement
Learn more about this trial
A Single and Repeated Dose Escalation of RBD1016 in Subjects With Chronic Hepatitis B Virus (HBV) Infection
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