Clinical Study to Evaluate the Efficacy and Safety of HH-006 in Patients With Chronic Hepatitis B Virus Infection

Phase II Clinical Study to Evaluate the Efficacy and Safety of Multiple Dosing of HH-006 in Patients With Chronic Hepatitis B Virus Infection

Study HH006-202 is designed to assesses the efficacy and safety of HH-006 in adults chronic HBV infection. Eligible participants will receive study treatment for 48 weeks. All treated patients will also undergo a follow-up period after last study drug treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Hepatitis B Virus Infection
• Intervention / Treatment: Biological: HH-006

Detailed Description

This is a multicenter, open-label Phase II clinical study, It aims to evaluate the efficacy, safety, and tolerability of HH-006 in untreated HBeAg-positive/negative chronic HBV infected individuals and those with HBeAg-negative chronic HBV infection who have been treated with NAs for more than one year.

Study participants will undergo various screening examinations as per the protocol before enrollment. Eligible participants will be assigned to Cohort 1, Cohort 2, or Cohort 3 according to different inclusion and exclusion criteria (see Inclusion/Exclusion Criteria for details). Upon entering the study, participants in all cohorts will start a 4-week loading dose period of HH-006 480 mg QW, followed by HH-006 240 mg QW for 44 weeks. Participants in Cohort 3 will continue their pre-existing NAs therapy after enrollment. Evaluations will include changes in HBsAg/HBV DNA/ALT and safety.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaoping Chen PM; Phone Number: +86 18518676059; Email: chenxiaoping@hhhbio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Sex: male or female; Age: 18 to 45 years old (inclusive);
• Male body weight ≥ 50 kg, female body weight ≥ 45 kg, and body mass index (BMI): 18 kg/m² ≤ BMI ≤ 28 kg/m²;
• HBsAg and/or HBV DNA positivity for more than 6 months (including 6 months), or previous liver biopsy results indicating chronic hepatitis B, or negative for anti-HBc IgM;
• Virological and liver function indicators at screening:

Cohort 1: HBeAg-positive, 2000 IU/mL ≤ HBsAg ≤ 100,000 IU/mL, HBV DNA > 105 IU/mL, 2 × upper limit of normal (ULN) ≤ ALT ≤ 8 × ULN; Cohort 2: HBeAg-negative, 100 IU/mL ≤ HBsAg ≤ 3000 IU/mL, 20 IU/mL < HBV DNA ≤ 2000 IU/mL, ALT ≤ 5 × ULN; Cohort 3: HBeAg-negative, 100 IU/mL ≤ HBsAg ≤ 3000 IU/mL, HBV DNA ≤ 100 IU/mL, ALT ≤ 2 × ULN;

• Previous antiviral treatment:

Cohort 1 and Cohort 2: No interferon antiviral treatment within the past 1 year, and no nucleos(t)ide analogue (NA) treatment within the 6 months prior to screening; Cohort 3: No interferon antiviral treatment within the past 1 year; received only nucleos(t)ide analogue monotherapy for at least one year;

• Fully understand the study content, procedures, and possible adverse reactions, and sign the written informed consent form (ICF);
• Able to communicate effectively with the investigator and complete the study in accordance with the study requirements;
• Male subjects who have not undergone sterilization and female subjects who have been postmenopausal for less than two years must agree to take adequate and effective contraceptive measure from screening until the last follow-up visit.

Exclusion Criteria:

• Co-infected with hepatitis C, syphilis, or human immunodeficiency virus (HIV);
• At screening: total bilirubin ≥ 3 × ULN and direct bilirubin (DBil) > 1 × ULN; hemoglobin < 100 g/L; platelet count < 100,000/mm³ (100 × 109/L); absolute neutrophil count < 1,500/mm³ (1.5 × 109/L); serum albumin < 35 g/L; prothrombin time international normalized ratio (INR) > 1.3; glycated hemoglobin (HbA1c) ≥ 7%; estimated glomerular filtration rate (eGFR) (MDRD formula) < 60 mL/min/1.73 m² (Appendix 2 MDRD calculation formula);
• Clinically significant electrocardiogram (ECG) abnormalities (e.g., QTcF > 450 ms in males, > 470 ms in females, severe arrhythmias such as torsade de pointes, paroxysmal ventricular tachycardia, symptomatic atrial fibrillation/flutter requiring emergency treatment, complete atrioventricular block); poorly controlled or refractory hypertension (e.g., systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg after medication use, etc.);
• Concurrent clinically significant other liver diseases, including but not limited to: moderate or severe fatty liver, alcoholic liver disease, autoimmune liver disease, hereditary metabolic liver disease, drug-induced liver injury, etc.;
• History of progressive hepatic fibrosis or cirrhosis at any time prior to or during screening;
• Current or prior history of hepatic decompensation manifestations, including but not limited to: ascites, hepatic encephalopathy, esophageal and gastric variceal bleeding, hepatorenal syndrome, etc.;
• Previous history of hepatocellular carcinoma, or at screening: serum alpha-fetoprotein (AFP) ≥ 50 ng/mL; or liver ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) findings suggestive of possible hepatocellular carcinoma;

• Concurrent severe diseases or clinical conditions in other systems that, in the investigator's judgment, make the participant unsuitable for inclusion in this study:

  1. Circulatory system diseases: e.g., unstable angina, myocardial infarction, congestive heart failure, etc.;
  2. Respiratory system diseases: e.g., severe chronic obstructive pulmonary disease, etc.;
  3. Primary or secondary kidney diseases (e.g., chronic renal decompensation, renal diseases secondary to diabetes, hypertension, vascular diseases, etc.);
  4. Endocrine system diseases: e.g., poorly controlled diabetes or thyroid diseases, etc.;
  5. Autoimmune diseases: e.g., systemic lupus erythematosus, primary immune thrombocytopenia, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, autoimmune hemolytic anemia, severe psoriasis, etc.;
  6. Neuropsychiatric disorders: e.g., epilepsy, schizophrenia, depression, etc.;
  7. Malignant tumors;
• Lactating women or those with a positive pregnancy test;
• Persistent alcohol consumption (average daily intake > 40 g alcohol for males, > 20 g alcohol for females) or illicit drug abuse within 6 months prior to screening (including the screening period);
• Participation in any clinical trial of a drug (except for those who did not receive the investigational product) or medical device (except for non-invasive medical devices) within 3 months prior to screening;
• Major trauma or major surgery within the past three months;
• History of allergy to HH-003, HH-006, or polysorbate 80;
• In the investigator's judgment, unsuitability for participation in this study, or close relationship with the study site: e.g., immediate family members of the investigator, or affiliated personnel (e.g., site staff or students).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HH-006 Cohort 1; untreated HBeAg-positive chronic HBV infected participants will receive HH-006	Biological: HH-006; HH-006 480 mg SC injection every one week for 4 weeks and followed by 240 mg QW for 44 weeks
Experimental: HH-006 Cohort 2; untreated HBeAg-negative chronic HBV infected participants will receive HH-006	Biological: HH-006; HH-006 480 mg SC injection every one week for 4 weeks and followed by 240 mg QW for 44 weeks
Experimental: HH-006 Cohort 3; participants with HBeAg-negative chronic HBV infection who have been treated with NAs for more than one year will receive HH-006	Biological: HH-006; HH-006 480 mg SC injection every one week for 4 weeks and followed by 240 mg QW for 44 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBsAg change from baseline	value of HBsAg change from baseline	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration Versus Time Curve (AUC)	AUC of HH-006 in plasma	up to 24 weeks follow-up
Maximum Plasma Concentration (Cmax)	Cmax of HH-006 in plasma	up to 24 weeks follow-up
Time to Reach Maximum Plasma Concentration (Tmax)	Tmax of HH-006 in plasma	up to 24 weeks follow-up
Apparent Terminal Elimination Half-life (T1/2)	T1/2 of HH-006 in plasma	up to 24 weeks follow-up
Apparent Plasma Clearance (CL/F)	CL/F of HH-006 in plasma	up to 24 weeks follow-up
HBsAg change from baseline	value of HBsAg change from baseline	week 12, week 48 of treatment and week 24 of follow up
proportion of HBsAg loss	number of participants with HBsAg loss	week 24, week 48 of treatment and week 24 of follow up
HBsAg change from baseline	value of HBsAg change from baseline	up to 72 weeks
cohort 1and cohort 2: proportion of HBV DNA decreasing more than 1 log10/mL	number of participants with HBV DNA decreasing more than 1 log10/mL	week 12, week 24, week 48 of treatment and week 24 of follow up
proportion of HBV DNA < LLOQ	number of participants with HBV DNA < LLOQ	week 12, week 24, week 48 of treatment and week 24 of follow up
HBV DNA change from baseline	value of HBV DNA change from baseline	up to 72 weeks
proportion of ALT normalization	number of participants with ALT normalization	week 12, week 24, week 48 of treatment and week 24 of follow up
ALT change from baseline	value of ALT change from baseline	up to 72 weeks
proportion of HBsAg seroconversion	number of participants with HBsAg seroconversion	week 12, week 24, week 48 of treatment and week 24 of follow up
cohort1: proportion of HBeAg seroconversion	number of participants with HBeAg seroconversion	week 12, week 24, week 48 of treatment and week 24 of follow up
cohort1: HBeAg change from baseline	value of HBeAg change from baseline	up to 72 weeks
LSM change from baseline	value of LSM change from baseline	week 24, week 48 of treatment and week 24 of follow up
Apparent volume of distribution (Vd/F)	Vd/F of HH-006 in plasma	up to 24 weeks follow-up
Incidence of adverse events (AEs) and serious adverse events (SAEs)	Number of subjects with adverse events (AEs) and serious adverse events (SAEs) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	up to 72 weeks
Clinically significant abnormalities	Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.	up to 72 weeks follow-up
Titers of Anti-drug Antibody (ADA)	ADA analysis of HH-006	up to 72 weeks

Collaborators and Investigators

• Sponsor: Huahui Health

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2026
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): March 22, 2028

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 2, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: chronic hepatitis B virus infection
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: HH006-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No