A Study of RBD1016 in CHB Participants

Study Overview
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Brief Summary
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This study consists of Part A and Part B. Part A is a multi-center, randomized, double-blind, placebo-controlled clinical study to assess the safety, efficacy, PK and immunogenicity of RBD1016 injection combined with NAs in CHB participants. Part B is a multi-center, open clinical study to assess the safety, efficacy, PK and immunogenicity of RBD1016 injection combined with PegIFN-α and NAs in CHB participants.

Detailed Description
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The study consists of screening period, treatment period, and follow up period. Part A is divided into 3 dose groups, namely 100 mg Q4W, 200 mg Q4W and 200 mg Q12W. Each group will enroll 28 eligible participants, with 21 participants receiving RBD1016 injection and 7 participants receiving placebo. Part B has a RBD1016 200mg dose group, which will enroll 20 participants to receive RBD1016 combined with PegIFN-α and NAs treatment.

Official Title
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A Phase II Clinical Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of RBD1016 Injection in Participants With Chronic Hepatitis B

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: RBD1016
* Drug: RBD1016+PegIFN-α


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give written informed consent for study participation; Male or female participants aged 18-65 years; Body mass index (BMI) within the range of 18-34 kilograms/square meter (kg/m2); Documented history of chronic hepatitis B virus (HBV) infection, by positive HBsAg and/or HBV DNA tests ≥ 6 months before screening; HBeAg positive or negative at screening; On a stable regimen (≥ 12 months before screening) of any approved first-line oral NAs; Serum alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal (ULN); Liver transient elastography (FibroScan) results within 12 months before screening or at screening showing that the liver stiffness measurement (LSM) level is less than 9 kPa; or with liver biopsy within 24 months before screening showing that the Metavir score is F0-F2. Exclusion Criteria: Diagnosed with other liver diseases other than hepatitis B; History of liver cirrhosis or hepatic decompensation (e.g., ascites, varices bleeding, or hepatic encephalopathy) before or at screening; History of organ transplantation or previous or concurrent with hepatocellular carcinoma (HCC), or imaging findings suggesting a possibility of malignant liver lesions; Concurrent hepatitis C virus (HCV), human immunodeficiency virus (HIV), or diagnosis of syphilis, acute hepatitis A or acute hepatitis E; Laboratory results at screening as follows: serum alpha-fetoprotein (AFP) >50 μg/L; serum albumin concentration <3.0 g/dL; international normalized ratio (INR) >1.5; platelet count <90×10^9/L; serum direct bilirubin (DB) >2×ULN; serum creatinine concentration >1.5×ULN or creatinine clearance <60 mL/min (according to the Cockcroft-Gault equation); or any clinically significant laboratory outliers that the investigator believes may interfere with the interpretation of the efficacy and safety data in this study; Those who the investigator believes are not suitable to participate in the study due to other factors. Additional exclusion criteria for Part B: Participants who are judged not to be suitable for IFN treatment for any reason; History of IFN treatment within 12 months prior to screening; Other situations that the investigator believes are not suitable to participate in Part B.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RBD1016/placebo 100 mg Q4W group<br>Participants in the 100 mg Q4W dose group will receive corresponding doses of RBD1016 injection or placebo by subcutaneous injection on D1, D29, D57, and D85. | Drug: RBD1016<br>* RBD1016 with NAs background treatment will be explored.<br>|
| Experimental: RBD1016/placebo 200 mg Q4W group<br>Participants in the 200 mg Q4W dose group will receive corresponding doses of RBD1016 injection or placebo by subcutaneous injection on D1, D29, D57, and D85. | Drug: RBD1016<br>* RBD1016 with NAs background treatment will be explored.<br>|
| Experimental: RBD1016/placebo 200 mg Q12W group<br>Participants in the 200 mg Q12W dose group will receive corresponding doses of RBD1016 injection or placebo by subcutaneous injection on D1, and D85. | Drug: RBD1016<br>* RBD1016 with NAs background treatment will be explored.<br>|
| Experimental: RBD1016+PegIFN-α 200 mg Q4W group<br>Participants in the 200 mg Q4W dose group will receive corresponding doses of RBD1016 injection by subcutaneous injection on D1, D29, D57, and D85, and also receive 180 µg PegIFN-α subcutaneously every week for 48 weeks | Drug: RBD1016+PegIFN-α<br>* RBD1016 with PegIFN-α and NAs background treatment will be explored.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety: number and percentage of AEs | Number and percentage of participants with adverse events (AEs). All reported AE terms will be coded using Medical Dictionary for Drug Regulatory Affairs (MedDRA). | 24 weeks | 
| efficacy: the maximum decline of HBsAg level | The maximum decline (log value) of HBsAg level. Electro chmiluminescence method will be used to detect hepatitis B surface antigen (HBsAg). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy: the proportion of HBsAg decline≥1 log10 IU/mL | The proportion of participants with HBsAg decline ≥1 log10 IU/mL. Electro chmiluminescence method will be used to detect HBsAg. | 24 weeks | 
| PK parameter Cmax | Maximum concentration (Cmax) will be calculated by PhoenixWinNonlin software (V8.0 or higher). | 12 weeks | 
| PK parameter Tmax | Time to maximum concentration (Tmax) will be calculated by PhoenixWinNonlin software (V8.0 or higher) will be used to calculate the PK parameter. | 12 weeks | 
| PK parameter AUC0-t | 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). | 12 weeks | 
| PK parameter t1/2 | Half-Life (t1/2) will be calculated by PhoenixWinNonlin software (V8.0 or higher). | 12 weeks | 
| PK parameter Vd/F | Apparent volume of distribution (Vd/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher). | 12 weeks | 
| PK parameter CL/F | Clearance (CL/F) will be calculated by PhoenixWinNonlin software (V8.0 or higher). | 12 weeks |