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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis D, Chronic; Hepatitis B Chronic Infection
• Intervention / Treatment: Drug: HepB mAb19

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ole Schmeltz Søgaard, MD, PhD, professor; Phone Number: +45 24 77 79 95; Email: olesoega@rm.dk
• Study Contact Backup: Name: Henriette Vendelbo Graversen, MD; Phone Number: +45 51 49 25 95; Email: henrgv@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Henriette Vendelbo Graversen, MD; Phone Number: +45 51 49 25 95; Email: henrgv@rm.dk
• Germany
  • Berlin, Germany
    • Not yet recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Christian Gaebler, Professor; Phone Number: xxxxxxxx; Email: christian.gaebler@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opel label; All participants will be included in this study arm	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Rate and severity of solicited adverse events that are Grade 2 or above	Two weeks after each administration
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.	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	From enrollment to end of follow-up at week 60
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.	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	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.	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	Assesment of HepB mAb19 elimination half-life (t1/2)	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	Assesment of clearance (CL/F) of HepB mAb19	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	Calculation of volume of distribution (Vz/F)	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	Calculation of area under the curve (AUC) for HepB mAb19	From enrollment to end of follow-up at week 60
Pharmacokinetic profile	Calculation of HepB mAb19 decay curve	From enrollment to end of follow-up at week 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virologic response	Virologic response defined as HDV RNA decrease of ≥2 log10 IU/mL or to undetectable from baseline (day 0) to week 28.	From baseline (day 0) to week 28
Anti-drug antibodies	Rate of induced anti-HepB mAb19 antibodies.	From enrollment to end of follow-up at week 60
Changes in liver function tests	Changes in liver function tests (e.g. ALT, AST, alkaline phosphatase, bilirubin, albumin) at selected follow-up visits.	From enrollment to end of follow-up at week 60

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to end of follow-up at week 60
HDV markers	- Anti-HDV at baseline and at selected follow-up visits.	From enrollment to end of follow-up at week 60
Innate immune response	Changes in innate immune responses following HepB mAb19 administration.	From enrollment to end of study at week 60
Changes in inflammatory markers	Changes in inflammatory markers following HepB mAb19 administration.	From enrollment to end of follow-up at week 60
Changes in fibrosis grade	Changes in fibrosis grade by FibroScan from entry to end of study.	From enrollment to end of follow-up at week 60.

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: SAMBA-D; 2025-522125-36-00 (EU CT no.)
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis D; Hepatitis D, Chronic
• Other Study ID Numbers: SAMBA-D-001; 2025-522125-36-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No