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.
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
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
Single group
HepB mAb19
DrugAll 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.
Safety and tolerability
Rate and severity of solicited adverse events that are Grade 2 or above
Safety and tolerability
Rate and severity of treatment-emerging unsolicited adverse events (including confirmed laboratory abnormalities) 2, 12, 28 and 60 weeks after first HepB mAb19 administration.
Safety and tolerability
Rate and severity of serious adverse events (SAEs) throughout the study period following investigational product (IP) administration
Safety and tolerability
Rate and severity of adverse events of special interest, such as immune complex disease (ICD) throughout the study period following IP administration.
Virologic response
Virologic response defined as HDV RNA decrease of ≥2 log10 IU/mL or to undetectable from baseline (day 0) to week 28.
Anti-drug antibodies
Rate of induced anti-HepB mAb19 antibodies.
Changes in liver function tests
Changes in liver function tests (e.g. ALT, AST, alkaline phosphatase, bilirubin, albumin) at selected follow-up visits.
HBV markers
* Change in quantitative serum HBsAg levels from baseline (day 0) and from achieved nadir (lowest serum HBsAg level following IP administration) at each scheduled follow up visit. * HBV DNA levels at baseline and selected follow up visits * HBcrAg levels at baseline and selected follow up visits. * HBsAb conversion from negative at baseline to positive at selected follow up visits. * HBeAg levels at baseline and selected follow up visits. * HBeAb conversion from negative at baseline to positive at selected follow up visits, among participants who are seronegative at baseline. * HBV-specific T and B cell immune responses following HepB mAb19 administration.
HDV markers
\- Anti-HDV at baseline and at selected follow-up visits.
Innate immune response
Changes in innate immune responses following HepB mAb19 administration.
Changes in inflammatory markers
Changes in inflammatory markers following HepB mAb19 administration.
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Aarhus University Hospital
Lead sponsor
University of Aarhus
Sponsor institution
Charite University, Berlin, Germany
Collaborator
