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

Official title

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

Overview

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.

Interventions

• Drug HepB mAb19
  All participants will receive a dose of HepB mAb19 at day 0 of 10 mg/kg and at day 28 of 30 mg/kg. They will receive a third dose at day 140 of 30 mg/kg if we observe a 1-log decrease in HDV RNA from week 0 to week 6.

Primary outcome measures

• Safety and tolerability [Time frame: Two weeks after each administration]
• Safety and tolerability [Time frame: 2, 12, 28 and 60 weeks after first HepB mAb19 administration]
• Safety and tolerability [Time frame: From enrollment to end of follow-up at week 60]
• Safety and tolerability [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]
• Pharmacokinetic profile [Time frame: From enrollment to end of follow-up at week 60]

Secondary outcome measures (3)

• Virologic response [Time frame: From baseline (day 0) to week 28]
• Anti-drug antibodies [Time frame: From enrollment to end of follow-up at week 60]
• Changes in liver function tests [Time frame: From enrollment to end of follow-up at week 60]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 1 center

• Aarhus University Hospital — Aarhus

Germany · 1 center

• Charité - Universitätsmedizin Berlin — Berlin

Identifiers

NCT: NCT07610772 · SAMBA-D-001 · 2025-522125-36-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗