Safety and Antiviral Activity of a Monoclonal Hepatitis B Antibody: a Phase 1b, Open-label Trial in Individuals With Chronic Hepatitis D Infection

Aarhus University Hospital

Status and phase

Enrolling

Phase 1

Conditions

Hepatitis D, Chronic

Hepatitis B Chronic Infection

Treatments

Drug: HepB mAb19

Study type

Interventional

Funder types

Other

Identifiers

NCT07610772

2025-522125-36-00 (EU Trial (CTIS) Number)

SAMBA-D-001

Details and patient eligibility

About

Hepatitis D virus (HDV) is a major global health issue, with an estimated 12 million people living with the infection worldwide. HDV infection requires the presence of hepatitis B virus (HBV), as it relies on hepatitis B virus for replication within the liver cells. Treatment options for HDV are limited and cannot cure the infection. The combination of concurrent HBV and HDV increases the risk of developing severe liver disease, including cirrhosis and liver cancer. This risk would significantly decrease if HDV is eliminated or reduced. Consequently, there is a need for the development of new treatment options.

Colleagues at Rockefeller University in New York have identified the antibody HepB mAb19, which effectively reduces the amount of circulating HBV antigens. Since HDV depends on HBV to replicate, we will test this antibody as a potential treatment for HDV.

The trial design is a phase 1b open-label aiming at including 15 study participants with chronic hepatitis D infection. All study participants will receive two or three dosis of the antibody, HepB mAB19, and will be followed for 60 weeks after the first HepB mAb19 infusion.

This study will evaluate the safety and pharmacokinetics of this antibody, as well as its potential effects on viral levels of HDV RNA and antiviral immune responses in individuals living with chronic HDV infection.

Enrollment

15 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

HDV infection confirmed by positive anti-HDV antibody and detectable HDV RNA
HBs antibody negative during screening period
Both HBeAg positive and negative participants are included
Ability and willingness to provide informed consent
Participants who can become pregnant must agree to use two methods of contraception:
Participants who can impregnate a partner and who are engaging in sexual activity that could lead to pregnancy must agree to use condoms 10 days prior to study entry and during study follow up to avoid impregnating a partner who can get pregnant.

Exclusion criteria

Child-Turcotte-Pugh >9 points
Severe clinical hepatic decompensation-such as hepatic encephalopathy or variceal hemorrhage-occurring currently or within the past 12 months.
Any confirmed significant allergic reactions (urticaria or anaphylaxis) against monoclonal antibody or vaccine, or multiple drug allergies (non-active hay fever is acceptable)
Pregnancy or lactation
Any vaccination 2 weeks prior to entry
Prior receipt of HepB mAb19 therapy
Any significant acute infection (e.g. influenza, COVID-19) or any other clinically significant illness 2 weeks prior to entry
Active hepatitis C infection
Untreated HIV disease
Individuals with HIV receiving antiretroviral therapy who have had a measurement of plasma HIV RNA (viral load) >50 copies/mL within the past 6 months are excluded. However, a single viral load measurement between >50 and <500 copies/mL during this period is acceptable.
Participation in another clinical study of an investigational product currently or 12 weeks prior to entry, or expected participation during this study

Laboratory abnormalities in the parameters listed below:

Alpha fetoprotein >100 ng/mL
Hemoglobin <10 gm/dL (6.21 mmol/L)
Platelet count <25,000 /mm3
Estimated glomerular filtration rate (eGFR) <60 mL/min
ALT ≥ x10 upper limit of normal (ULN)

Current, or history of:

Clinical cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure.
Presence of clinically significant ECG abnormalities based on the average of the triplicate ECG recordings (e.g., PR interval >210 ms (1st degree AV block only if clinical symptoms are present), QT corrected for heart rate using the Fridericia's correction factor [QTcF] > 450 ms for males and QTcF >470 ms for females);
Chronic liver disease from another cause, ICD, or autoimmune diseases that in the opinion of the investigator would preclude participation
History of hematopoietic stem cell transplant or solid organ transplant