Clinical trial NCT05861674: A Study to Assess Efficacy and Safety of HH-003 Injection in Subjects With Chronic Hepatitis Delta Virus Infection
Official title: A Multicenter, Randomized, Controlled, Open-label Phase IIb Study to Assess Efficacy and Safety of HH-003 Injection in Subjects With Chronic Hepatitis Delta Virus Infection
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Chronic Hepatitis Delta Virus Infection
Lead sponsor: Huahui Health
Sponsor class: INDUSTRY
First posted: 2023-05-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, controlled, open-label, Phase IIb study of HH-003 injection, HH-003 injection is a monoclonal antibody targeting Hepatitis B virus. This study aims to assess efficacy and safety in subjects with chronic hepatitis delta virus infection.


Eligibility criteria: Inclusion Criteria:

* Signed the informed consent form;
* Male or female aged 18 to 70 years;
* Positive HBsAg at screening;
* History of chronic HDV infection for at least 6 months prior to randomization. For subjects also recommended for anti-HBV therapy, previous first line NrtIs treatment (ETV, TDF, TAF) within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take first line NrtIs treatment for at least 12 weeks prior to the planned start of study treatment is required;
* Positive HDV antibody at screening;
* HDV RNA ≥100 IU/mL at screening;
* 1×ULN\<Alanine aminotransferase (ALT) \<10×ULN at screening;

Exclusion Criteria:

* Subjects with known hypersensitivity to HH-003 and its components, history of severe allergic reaction to other therapeutic antibodies or severe allergic diseases;
* Subjects with contraindications for TAF;
* History of interferon therapy within 3 months before randomization;
* Any of the following lab test results at screening:

  1. Total bilirubin \>2×ULN (except for subjects with Gilbert syndrome);
  2. Direct bilirubin \> 1.5×ULN ;
  3. Platelets\<80,000/mm3 (80×109/L);
  4. Serum Albumin \<35 g/L;
  5. Prothrombin time international normalized ratio (INR) \>1.3;
  6. Hemoglobin \<100 g/L;
  7. Absolute neutrophils\<1,500/mm3 (1.5×109/L);
  8. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 (according to the calculation equation of CKD-MDRD);
* Concomitant decompensated cirrhosis (cirrhosis with complications of portal hypertension and/or decreased hepatic function). The diagnosis of cirrhosis is based on, but not limited to: liver imaging assessment within 6 months prior to randomization (including screening period) (e.g.: liver ultrasound) or cirrhosis indicated by histopathology of liver biopsy, or liver stiffness measurement LSM≥17 kPa at screening, refer to more serious reported findings;
* Hepatic insufficiency within 3 months prior to randomization (including but not limited to: ascites, hepatic encephalopathy, upper gastrointestinal hemorrhage);
* Previous or current hepatocellular carcinoma (HCC) or suspicion for HCC suggested by liver histopathology or liver imaging; or serum alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening;
* Subjects with history of alcoholic liver disease, nonalcoholic steatohepatitis, autoimmune liver disease or other hereditary liver diseases, drug-induced liver disease or other clinically significant chronic liver diseases not caused by HDV/HBV;
* History of other malignancies other than HCC, unless the subject's malignancy has been in complete remission within 3 years prior to screening and does not require chemotherapy and additional medical or surgical intervention; invasive medical devices within 1 month before randomization.

Primary outcomes:
measure: Proportion of subjects with serum HDV RNA below the lower limit of detection or a decrease of ≥2 log10 IU/mL from baseline and ALT normalization
timeFrame: At Week 24 of the treatment period
Secondary outcomes:
measure: Proportion of subjects with serum HDV RNA below the lower limit of detection or a decrease of ≥2 log10 IU/mL from baseline
timeFrame: At Week 24 of the treatment period
measure: Proportion of subjects with ALT normalization
timeFrame: At Week 24 of the treatment period
measure: Change from baseline in liver stiffness measurement (LSM)
timeFrame: At Week 24 of the treatment period
measure: Proportion of subjects with serum HDV RNA below the lower limit of detection or a decrease of ≥2 log10 IU/mL from baseline and ALT normalization
timeFrame: At Week 48 of the treatment period
measure: Proportion of subjects with serum HDV RNA below the lower limit of detection or a decrease of ≥2 log10 IU/mL from baseline
timeFrame: At Week 48 of the treatment period
measure: Proportion of subjects with ALT normalization
timeFrame: At Week 48 of the treatment period
measure: Change from baseline in liver stiffness measurement (LSM)
timeFrame: At Week 48 of the treatment period
measure: Proportion of subjects with serum HDV RNA below the lower limit of detection or a decrease of ≥2 log10 IU/mL from baseline
timeFrame: At Week 24 of the follow-up period
measure: Proportion of subjects with ALT normalization
timeFrame: At Week 24 of the follow-up period
measure: Change from baseline in liver stiffness measurement (LSM)
timeFrame: At Week 24 of the follow-up period
measure: Change from baseline in serum HDV RNA levels at different time points
timeFrame: Up to Week 72
measure: Change from baseline in serum ALT levels at different time points
timeFrame: Up to Week 72
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital Captial Medical University
state: Beijing
Study officials:
References: