HepBTer: From fungus to virus, a phase 2a clinical trial investigating the safety and efficacy of terbinafine in chronic hepatitis B patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

25 Jul 2024 → 21 Aug 2025

Decision date (initial)

2024-07-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514888-25-00

EudraCT number

2019-003419-68

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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.

Conditions and MedDRA coding

Chronic hepatitis B

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) Age 18 – 60 years 2) Proven CHB for more than 6 months, based on serology (HBsAg positivity) and at screening a viral load of: i) Group A: HBV DNA ≥200 IU/mL and <20,000 IU/mL ii) Group B: HBV DNA < 20 IU/mL 3) HBeAg-positive or HBeAg-negative 4) No current use of any antiviral medication (group A) or currently treated with tenofovir only, for > 6 months (group B). 5) Normal liver function tests, assessed as follows: i) Liver stiffness measurement using Fibroscan® of ≤ 7.0 kiloPascal (kPa) ii) Alanine aminotransferase (ALT) and/or aspirate aminotransferase (AST) at screening ≤ 1.25 x upper limit of normal (ULN) iii) Thrombocytes 150-400 10E9/L iv) Total bilirubin 0-17 µmol/L (elevated levels may be accepted if unconjugated portion is elevated in patients with Gilbert syndrome) v) Albumin within normal value (35 – 50 g/L) vi) Prothrombin Time (PT) within normal value (9,5 - 12.5 sec) vii) Alkaline phosphatase (ALP) and Gamma-glutamyltransferase (GGT) within normal values (40-120 U/L and 0-40 U/L respectively) 6) Body mass index (BMI): 17.0-35.0 kg/m2 7) Clinical chemistry, hematologic and coagulation tests at screening must be within normal limits or clinically non-significant, as by the investigator’s assessment. 8) At screening, women of child bearing potential must be non-pregnant and non-lactating; a urine or serum pregnancy test will be performed at screening. 9) Female patients of child-bearing potential (with a fertile male sexual partner) and male patients (if not surgically sterilized) must be willing to use adequate contraception from screening until last study visit. 10) No recent (<3 months) history of any clinically significant conditions, which, in the opinion of the investigator, would jeopardize the safety of the patient or impact the validity of the study results. 11) Written informed consent must be obtained before any study related interventions (including screening and enrollment) can be conducted.

Exclusion criteria 1

1. 1) Currently active, or a history of liver cirrhosis determined by one or more of the following: i) Liver biopsy; ii) Elastography (e.g. Fibroscan); iii) Combination of usual radiological and biochemical criteria 2) Currently active liver disease other than CHB 3) Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV) and/or human immunodeficiency virus (HIV) 4) Acute hepatitis A virus (HAV) infection at screening 5) Renal impairment (estimated glomerular filtration rate (eGRF) < 60ml/min) 6) Currently active, or a history of, psoriasis or lupus erythematodes 7) Use of oral medication that interacts with the liver metabolism enzyme CYP2D6, or which is known to be hepatotoxic or otherwise known to interact with terbinafine (such as rifampicine). 8) The use of a L-type calcium (LTCC) blocker (such as lomerizine of nifedipine), since these may interact with the HBV transcription according to the article by Klundert et al. 9) Usage or plans to receive systemic immunosuppressive or immunomodulating medication (e.g. IFN) during the study or ≤4 months prior to the first investigational product administration. 10) Clinical diagnosis of substance abuse ≤12 months prior to screening with narcotics or cocaine or with alcohol (regular consumption >14 units/week [men] and >7 units/week [women]) 11) Inability to understand the patient information and make an informed decision to participate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Decline in level of serum HBsAg >0.32log10 IU/mL in both groups A and B (week 10 vs baseline) - Decline in serum HBV DNA >0.86log10 in group A at the end of study treatment (week 10 vs baseline)

Secondary endpoints 1

1. - Safety and tolerability of terbinafine as mono- or combination therapy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

Hadassa Porretta

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Hadassa Porretta

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications