The primary objective of this study is to evaluate the efficacy of bulevirtide administered subcutaneously (SC) for 48 weeks at a dose of 2 mg or 10 mg once daily for treatment of chronic hepatitis delta (CHD) in comparison to delayed treatment. The main goal of this study is to determine the effectiveness of bulevirtide in participants randomized to bulevirtide 2 mg or 10 mg once daily SC as compared to participants randomized to delayed treatment for 48 weeks. Treatment will continue through Week 144 (participants randomized to delayed treatment will change to bulevirtide 10 mg once daily SC after Week 48 through Week 144). All participants will be followed off-treatment for an additional 96 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
Administered via SC injections
New York University School of Medicine, an administrative unit of New York University, an education corporation
New York, New York, United States
Cornell University Well Madical College
New York, New York, United States
Universitätsklinikum Essen (AoR), Klinik für Gastroenterologie und Hepatologie
Essen, Germany
Universitätsklinikum Frankfurt Medizinische Klinik 1
Frankfurt am Main, Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
Hanover, Germany
Heidelberg University Hospital, Departament of Gastroenterology, Infectious Diseases, Intoxication
Heidelberg, Germany
Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, Italy
Università di Modena e Reggio Emilia- Ospedale Civile S.
Modena, Italy
U.O. Epatologia - Azienda Ospedaliero Universitaria Pisana
Pisa, Italy
...and 9 more locations
Percentage of Participants With Combined Response at Week 48
Combined response was defined as fulfilment of two conditions simultaneously: Undetectable (\< lower limit of quantification (LLOQ, target not detected)) HDV RNA or decrease by ≥ 2 log10 IU/mL from baseline; and ALT normalization.
Time frame: Week 48
Percentage of Participants With Undetectable HDV RNA at Week 48
Undetectable HDV RNA at Week 48 means undetectable (\< LLOQ, target not detected) HDV RNA at Week 48.
Time frame: Week 48
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Week 48
ALT normalization was defined as an ALT value within the normal range, based on the central laboratories \[Russian sites: ≤ 31 U/L for females and ≤ 41 U/L for males; all other sites: ≤ 34 U/L for females and ≤ 49 U/L for males\])
Time frame: Week 48
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 48
ANCOVA was used for analysis.
Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 48
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 96
Mixed model for repeated measurements (MMRM) was used for analysis.
Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 96
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 144
MMRM was used for analysis.
Time frame: Baseline, Week 144
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 192
MMRM was used for analysis.
Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 192
Change From Baseline in Liver Stiffness, as Measured by Elastography at Week 240
MMRM was used for analysis.
Time frame: Baseline (Baseline for Delayed Treatment/Bulevirtide 10 mg/day is reset at Week 48), Week 240
Percentage of Participants With Undetectable HDV RNA 24 Weeks After Scheduled End of Treatment (Sustained Virological Response)
Undetectable HDV RNA 24 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 168
Time frame: Week 168
Percentage of Participants With Undetectable HDV RNA 48 Weeks After Scheduled End of Treatment (Sustained Virological Response)
Undetectable HDV RNA 48 Weeks after Scheduled End of Treatment means undetectable (\< LLOQ, target not detected) HDV RNA at Week 192
Time frame: Week 192
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event (AE) by Week 144
An AE was defined as any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with the study drug. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not related to the study drug.
Time frame: Delayed Treatment/Bulevirtide 10 mg/day arm: Week 48 up to Week 144; Bulevirtide 2mg/day and 10 mg/day arms: First dose date up to Week 144
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