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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

Study summary

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.

Eligibility

Primary outcome measure(s)

• Safety and tolerability — Two weeks after each administration
  Rate and severity of solicited adverse events that are Grade 2 or above
• Safety and tolerability — 2, 12, 28 and 60 weeks after first HepB mAb19 administration
  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 — From enrollment to end of follow-up at week 60
  Rate and severity of serious adverse events (SAEs) throughout the study period following investigational product (IP) administration
• Safety and tolerability — From enrollment to end of follow-up at week 60
  Rate and severity of adverse events of special interest, such as immune complex disease (ICD) throughout the study period following IP administration.
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  HepB mAb19 levels in serum will be measured by a validated sandwich ELISA method developed and performed by Celldex Therapeutics. HepB mAb19 levels will be measured before and at the end of each of the antibody administrations, at 3 and 6 hours, and at later time points during follow up.
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  Assesment of HepB mAb19 elimination half-life (t1/2)
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  Assesment of clearance (CL/F) of HepB mAb19
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  Calculation of volume of distribution (Vz/F)
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  Calculation of area under the curve (AUC) for HepB mAb19
• Pharmacokinetic profile — From enrollment to end of follow-up at week 60
  Calculation of HepB mAb19 decay curve

Trial sites (2)

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