Hepatitis B Chronic Infection, Hepatitis D, Chronic
Conditions
Keywords
SAMBA-D, 2025-522125-36-00 (EU CT no.)
Brief 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.
Interventions
DRUGHepB 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.
Sponsors
Aarhus University Hospital
Charite University, Berlin, Germany
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability | Two weeks after each administration | Rate and severity of solicited adverse events that are Grade 2 or above |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic response | From baseline (day 0) to week 28 | 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 | From enrollment to end of follow-up at week 60 | Rate of induced anti-HepB mAb19 antibodies. |
| Changes in liver function tests | From enrollment to end of follow-up at week 60 | Changes in liver function tests (e.g. ALT, AST, alkaline phosphatase, bilirubin, albumin) at selected follow-up visits. |
Countries
Denmark, Germany
Contacts
CONTACTOle Schmeltz Søgaard, MD, PhD, professor
CONTACTHenriette Vendelbo Graversen, MD
Outcome results
None listed