- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07610772
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.
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Ole Schmeltz Søgaard, MD, PhD, professor
- Telefonní číslo: +45 24 77 79 95
- E-mail: olesoega@rm.dk
Studijní záloha kontaktů
- Jméno: Henriette Vendelbo Graversen, MD
- Telefonní číslo: +45 51 49 25 95
- E-mail: henrgv@rm.dk
Studijní místa
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Aarhus, Dánsko, 8000
- Nábor
- Aarhus University Hospital
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Kontakt:
- Henriette Vendelbo Graversen, MD
- Telefonní číslo: +45 51 49 25 95
- E-mail: henrgv@rm.dk
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Berlin, Německo
- Zatím nenabíráme
- Charité - Universitätsmedizin Berlin
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Kontakt:
- Christian Gaebler, Professor
- Telefonní číslo: xxxxxxxx
- E-mail: christian.gaebler@charite.de
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Opel label
All participants will be included in this study arm
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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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Safety and tolerability
Časové okno: Two weeks after each administration
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Rate and severity of solicited adverse events that are Grade 2 or above
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Two weeks after each administration
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Safety and tolerability
Časové okno: 2, 12, 28 and 60 weeks after first HepB mAb19 administration
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Rate and severity of treatment-emerging unsolicited adverse events (including confirmed laboratory abnormalities) 2, 12, 28 and 60 weeks after first HepB mAb19 administration.
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2, 12, 28 and 60 weeks after first HepB mAb19 administration
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Safety and tolerability
Časové okno: From enrollment to end of follow-up at week 60
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Rate and severity of serious adverse events (SAEs) throughout the study period following investigational product (IP) administration
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From enrollment to end of follow-up at week 60
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Safety and tolerability
Časové okno: From enrollment to end of follow-up at week 60
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Rate and severity of adverse events of special interest, such as immune complex disease (ICD) throughout the study period following IP administration.
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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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.
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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Assesment of HepB mAb19 elimination half-life (t1/2)
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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Assesment of clearance (CL/F) of HepB mAb19
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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Calculation of volume of distribution (Vz/F)
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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Calculation of area under the curve (AUC) for HepB mAb19
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From enrollment to end of follow-up at week 60
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Pharmacokinetic profile
Časové okno: From enrollment to end of follow-up at week 60
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Calculation of HepB mAb19 decay curve
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From enrollment to end of follow-up at week 60
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Virologic response
Časové okno: From baseline (day 0) to week 28
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Virologic response defined as HDV RNA decrease of ≥2 log10 IU/mL or to undetectable from baseline (day 0) to week 28.
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From baseline (day 0) to week 28
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Anti-drug antibodies
Časové okno: From enrollment to end of follow-up at week 60
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Rate of induced anti-HepB mAb19 antibodies.
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From enrollment to end of follow-up at week 60
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Changes in liver function tests
Časové okno: From enrollment to end of follow-up at week 60
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Changes in liver function tests (e.g.
ALT, AST, alkaline phosphatase, bilirubin, albumin) at selected follow-up visits.
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From enrollment to end of follow-up at week 60
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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HBV markers
Časové okno: From enrollment to end of follow-up at week 60
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From enrollment to end of follow-up at week 60
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HDV markers
Časové okno: From enrollment to end of follow-up at week 60
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- Anti-HDV at baseline and at selected follow-up visits.
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From enrollment to end of follow-up at week 60
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Innate immune response
Časové okno: From enrollment to end of study at week 60
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Changes in innate immune responses following HepB mAb19 administration.
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From enrollment to end of study at week 60
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Changes in inflammatory markers
Časové okno: From enrollment to end of follow-up at week 60
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Changes in inflammatory markers following HepB mAb19 administration.
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From enrollment to end of follow-up at week 60
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Changes in fibrosis grade
Časové okno: From enrollment to end of follow-up at week 60.
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Changes in fibrosis grade by FibroScan from entry to end of study.
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From enrollment to end of follow-up at week 60.
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Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- SAMBA-D-001
- 2025-522125-36-00 (Ctis)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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