Observational Study to Evaluate Efficacy, Safety and Biomarkers of Bulevirtide Treatment in Patients with Chronic hepatitis D

简要总结

主要结局

次要结局

• Percentage of patients with virological response of HDV RNA < LoD at month 1, 3 and every 3 months during treatment, and FU month 3, 6 and 9 after EOT.
• Percentage of patients with HBsAg < LoD at month 1 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.
• Change of HBsAg from baseline every 3 months during study period.
• Percentage of patients with HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline, at month 1 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with virological relapse, defined as HDV RNA < LoD at EOT and increase of HDV RNA to > LoD after EOT, after EOT, at FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with appearance of hepatitis B surface antibody (anti-HBs) at EOT, and FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with HBV DNA level < LoD every 3 months during study period.
• Percentage of patients with biochemical response, defined as normalization of alanine transaminase (ALT), at month 1, 3 and every 3 months during treatment, and FU month 3, 6, 9 and 12 after EOT.
• Percentage of patients with combined response, defined as HDV RNA < LoD or HDV RNA reduction of at least 2 log10 compared to baseline and ALT normalization, at month 1, 2 and 3, and every 3 months after treatment start, and FU month 3, 6, 9 and 12 after EOT.
• Change of liver elasticity measurement level from baseline compared to the level at every 6 months during on-treatment, EOT, and FU month 6 and 12 after EOT
• Percentage of AE of special interest: 1. Liver-related event, defined as new diagnoses of liver cirrhosis, HCC, or hepatic decompensation (ascites, variceal bleeding or hepatic encephalopathy); 2. Event of ≥ grade 3 hematological AE (in IFN treated); 3. Event of thyroid disorder (in IFN treated); 4. Event of injection site reaction; 5. Event of≥ grade 3 ALT increase.
• Percentage of missed BLV doses during treatment.
• Percentage of patients with early discontinuation of treatment and the reasons.
• Percentage of patients with SAE.
• EXPLORATORY ENDPOINTS: Change of HBcrAg from baseline every 3 months during study period.
• Change of HBV RNA level from baseline every 3 months during study period.
• Change of fibrosis stage in pre-treatment liver biopsy, compared to fibrosis stage in on- or post-treatment liver biopsy.
• Change of inflammation grade in pre-treatment liver biopsy, compared to inflammation grade in on- or post-treatment liver biopsy.
• Change of quality of life pre-treatment from baseline, compared to every 6 months after treatment start, EOT and FU month 6 and 12.
• Change of innate or adaptive immunological marker/signature in PBMC from baseline, compared to month 1, 6, and every 6 months, EOT, FU month 6 and 12.
• Identification of any innate or adaptive immunological marker/signature in PBMC, associated with on- or off-treatment virological and/or biochemical response.
• Identification of any intrahepatic immune marker/signature in pre-treatment liver biopsy, associated with on-treatment or off-treatment virological and/or biochemical response
• Identification of any biomarker in serum, associated with on- or off-treatment virological and/or biochemical response.
• Identification of any changes in oral or fecal microbiome, or other features in saliva or feces from baseline during and after treatment.