Ignite Creation Date:
2024-05-06 @ 8:12 PM
Last Modification Date:
2024-10-26 @ 3:22 PM
Study NCT ID:
NCT06295328
Status:
RECRUITING
Last Update Posted:
2024-03-06
First Post:
2024-02-12
Brief Title:
From Fungus to Virus Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
From Fungus to Virus a Phase 1b Clinical Trial Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HepBTer
Brief Summary:
Rationale Currently there is no curative therapy available for patients that are chronically infected with the hepatitis B virus HBV Especially the presence of a viral reservoir of stable episomal covalently closed circular DNA cccDNA in the nucleus of infected hepatocytes poses a great challenge for the development of curative therapies HBV cccDNA acts as the template for production of viral proteins and HBV genomes In a preclinical study terbinafine an antifungal agent was identified as a potent and specific suppressor of HBx-mediated cccDNA transcription HBx is an accessory viral protein of HBV which has been proven to be essential for HBV replication and enhances replication at the transcriptional level in vivo The suppression of cccDNA transcription results in a strong reduction of the production of viral genomes RNA and DNA as well as viral proteins This will allow recovery of the immune system increase viral clearance and prevent replenishment of the cccDNA pool in the hepatocyte all contributing to cure chronic hepatitis B CHB
Objective to provide proof of concept for the inhibition of HBx mediated cccDNA transcription by terbinafine both as monotherapy and add-on therapy next to tenofovir Secondary outcomes will be the safety and tolerability of terbinafine in this specific group
Study design This pilot study is a stratified single center randomized double-blinded placebo-controlled dose-ascending proof of concept clinical trial
Study population patients chronically infected with the hepatitis B virus with a normal liver function and no signs of liver damage who do not use any antiviral medication group A n16 or are treated with tenofovir 6 months group B n16
Intervention Patients will be randomly allocated to daily oral treatment with terbinafine or a matched placebo either as monotherapy group A or as add-on therapy to tenofovir group B
Main study parametersendpoints Primary outcomes decline in level of serum HBsAg 032log10 IUmL in both groups A and B and decline in serum HBV DNA 086log10 in group A at the end of study treatment week 10 vs baseline Secondary outcomes 1 Safety and tolerability of terbinafine as mono- or combination therapy 2 level of serum HBsAg and HBV DNA at 3 months follow-up 3 decline of HBsAg levels over time all visits 4 HBV RNA large HBsAg LHBs HBcrAg levels and HBeAg status at baseline and end of study 4
Nature and extent of the burden and risks associated with participation benefit and group relatedness Patients participating in this study will undergo physical examinations and blood sample collections 13 samples and in total 4675 mL They will also be asked to fill in the HBQOL and EQ5D5L quality of life questionnaires and a medicine diary In total there will be 13 visits in the hospital of which 7 will be for blood collection only Terbinafine can induce liver damage 1 of 50000 to 120000 prescriptions LiverTox a weekly safety laboratory control is implemented in the visits to detect possible liver toxicity in an early stage and prevent liver damage
Objective to provide proof of concept for the inhibition of HBx mediated cccDNA transcription by terbinafine both as monotherapy and add-on therapy next to tenofovir Secondary outcomes will be the safety and tolerability of terbinafine in this specific group
Study design This pilot study is a stratified single center randomized double-blinded placebo-controlled dose-ascending proof of concept clinical trial
Study population patients chronically infected with the hepatitis B virus with a normal liver function and no signs of liver damage who do not use any antiviral medication group A n16 or are treated with tenofovir 6 months group B n16
Intervention Patients will be randomly allocated to daily oral treatment with terbinafine or a matched placebo either as monotherapy group A or as add-on therapy to tenofovir group B
Main study parametersendpoints Primary outcomes decline in level of serum HBsAg 032log10 IUmL in both groups A and B and decline in serum HBV DNA 086log10 in group A at the end of study treatment week 10 vs baseline Secondary outcomes 1 Safety and tolerability of terbinafine as mono- or combination therapy 2 level of serum HBsAg and HBV DNA at 3 months follow-up 3 decline of HBsAg levels over time all visits 4 HBV RNA large HBsAg LHBs HBcrAg levels and HBeAg status at baseline and end of study 4
Nature and extent of the burden and risks associated with participation benefit and group relatedness Patients participating in this study will undergo physical examinations and blood sample collections 13 samples and in total 4675 mL They will also be asked to fill in the HBQOL and EQ5D5L quality of life questionnaires and a medicine diary In total there will be 13 visits in the hospital of which 7 will be for blood collection only Terbinafine can induce liver damage 1 of 50000 to 120000 prescriptions LiverTox a weekly safety laboratory control is implemented in the visits to detect possible liver toxicity in an early stage and prevent liver damage
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None