A Study to Evaluate the Antiviral Activity and Safety of HH-003 Injection in Subjects With Chronic Hepatitis B and Hepatitis D Co-infection

Study Overview
=================
Brief Summary
-----------------
This is an open-label phase IIa study of HH-003 to evaluate its antiviral activity and safety in subjects with chronic hepatitis B and hepatitis D co-infection. HH-003 is a human monoclonal antibody targeting the pre-S1 domain of the HBV large envelope protein. It blocks engagement of preS1 with sodium taurocholate co-transporting polypeptide (NTCP), the cellular receptor for HBV/HDV.

Official Title
-----------------
An Open-label Phase IIa Study to Evaluate the Antiviral Effect and Safety of HH-003 Injection in Subjects With Chronic Hepatitis B and D Co-infection

Conditions
-----------------
Chronic Hepatitis B and Hepatitis D Co-infection

Intervention / Treatment
-----------------
* Biological: HH-003 20mg/kg
* Biological: HH-003 3mg/kg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent form; Male or female subjects aged from 18 to 70 years inclusively; 18 kg/m2≤BMI≤32 kg/m2, body weight ≥45 kg for men and ≥40 kg for women; Positive HBsAg, anti-HDV IgG antibody and HDV RNA at screening; Women of childbearing potential or male subjects with female partners of childbearing potential should agree to use an adequate and highly effective contraceptions from screening to the end of study or until 12 weeks after last dose of the study drug (whichever is longer). Exclusion Criteria: Be pregnant or lactating at screening; Subjects with decompensated liver cirrhosis; Subjects with liver dysfunction (including but not limited to ascites, hepatic encephalopathy and upper gastrointestinal bleeding) within 3 months prior to screening; Average daily alcohol consumption >40g for men and >20g for women or drug abuse within 6 months prior to screening; Subjects with other serious diseases that is inappropriate for study participation per the Investigator's or the Sponsor's discretion (including but not limited to serious cardiac or pulmonary disease, chronic or recurrent urinary disorders, uncontrolled diabetes and autoimmune diseases, epilepsy requiring treatment); History of hepatocellular carcinoma (HCC) or hepatocellular carcinoma suggested by liver histopathology or liver imaging; Interferon antiviral therapy within 1 year prior to screening.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HH-003 20mg/kg<br>HH-003 20mg/kg, intravenously, Q2W | Biological: HH-003 20mg/kg<br>* HH-003 20mg/kg Q2W intravenously for 24 weeks<br>|
| Experimental: HH-003 3mg/kg<br>HH-003 3mg/kg, intravenously, Q2W | Biological: HH-003 3mg/kg<br>* HH-003 3mg/kg Q2W intravenously for 24 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with HBV DNA Negativation or Decrease by ≥1 log10 from Baseline at Week 24 |  | Week 24 | 
| Percentage of Participants with HDV RNA Negativation or Decrease by ≥1 log10 from Baseline at Week 24 |  | Week 24 | 
| Change from Baseline in Serum HBsAg Levels at Week 24 |  | from baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with ALT normalization at week 24 |  | Week 24 | 
| Changes from Baseline in Serum HBsAg Levels during the Study Period |  | from baseline to Week 48 | 
| Changes from Baseline in Serum HBV RNA Levels during the Study Period |  | from baseline to Week 48 | 
| Changes from Baseline in Serum HBV DNA Levels during the Study Period |  | from baseline to Week 48 | 
| Changes from Baseline in Serum HDV RNA Levels during the Study Period |  | from baseline to Week 48 | 
| Changes from Baseline in Serum HBeAg Levels in HBeAg-positive Subjects at Screening |  | from baseline to Week 48 |