- ICH GCP
- Реестр клинических исследований США
- Клиническое испытание 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.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 1
Контакты и местонахождение
Контакты исследования
- Имя: Ole Schmeltz Søgaard, MD, PhD, professor
- Номер телефона: +45 24 77 79 95
- Электронная почта: olesoega@rm.dk
Учебное резервное копирование контактов
- Имя: Henriette Vendelbo Graversen, MD
- Номер телефона: +45 51 49 25 95
- Электронная почта: henrgv@rm.dk
Места учебы
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Berlin, Германия
- Еще не набирают
- Charité - Universitätsmedizin Berlin
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Контакт:
- Christian Gaebler, Professor
- Номер телефона: xxxxxxxx
- Электронная почта: christian.gaebler@charite.de
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Aarhus, Дания, 8000
- Рекрутинг
- Aarhus University Hospital
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Контакт:
- Henriette Vendelbo Graversen, MD
- Номер телефона: +45 51 49 25 95
- Электронная почта: henrgv@rm.dk
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: 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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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Safety and tolerability
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Virologic response
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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HBV markers
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Соавторы и исследователи
Спонсор
Соавторы
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Патологические процессы
- Хроническое заболевание
- Атрибуты болезни
- Инфекции
- РНК-вирусные инфекции
- Вирусные заболевания
- Заболевания пищеварительной системы
- Заболевания печени
- Гепатит, Вирусный, Человеческий
- Гепатит, хронический
- Гепатит
- Патологические состояния, признаки и симптомы
- Гепатит Д
- Гепатит D, хронический
Другие идентификационные номера исследования
- SAMBA-D-001
- 2025-522125-36-00 (Ктис)
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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