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

Recruiting

• Conditions: Chronic hepatitis B infection; viral infection of the liver; 10047438

• Registration Number: NL-OMON52526
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 32

Inclusion Criteria

1) Age 18 - 60 years
2) Proven chronic hepatitis B (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 and -negative CHB patients
4) No current use of any antiviral medication (group A) or currently treated
with tenofovir only.
5) Normal liver function, assessed by:
i) 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 investigators
assessment.
8) At screening, women of child bearing potential must be non-pregnant and
non-lactating proven by negative urine or serum pregnancy test 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) At screening, has no recent (<3 months) history of any clinically
significant conditions, which, in the opinion of the investigator, would
jeopardize the safety of the subject or impact the validity of the study
results.
11) Voluntary written informed consent must be obtained before any study
related interventions (including screening and enrollment) can be conducted.

Exclusion Criteria

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 HCV, HDV, HEV and/or HIV
4) Acute HAV 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) Usage or plans to receive systemic immunosuppressive or immunomodulating
medications (e.g. IFN) during the study or <= 4 months prior to the first
investigational product administration.
9) 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])
10) Inability to understand the patient information and make an informed
decision to participate

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective: provide proof of concept for the inhibition of HBx mediated<br /><br>cccDNA transcription by terbinafine by means of:<br /><br>- Decline in level of serum HBsAg >0.32 log10 IU/mL at the end of study<br /><br>treatment (week 10 vs baseline).<br /><br>- Decline in serum HBV DNA >0.86 log10 in group A (monotherapy) at the end of<br /><br>study treatment (week 10 vs baseline). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Objective(s): safety and tolerability of terbinafine and changes in<br /><br>alternative virology markers:<br /><br>- Level of serum HBsAg and HBV DNA at 3 months follow-up, all HBV RNA, large<br /><br>HBsAg (LHBs) HBcrAg levels, and HBeAg status (at baseline and end of study).<br /><br>- Safety and tolerability of terbinafine as mono- or combination therapy, based<br /><br>on serum markers including among others: ALT, AST, total bilirubin (if >17 µmol/<br /><br>L, add conjugated bilirubin), ALP, GGT, albumin, thrombocytes, prothrombin time<br /><br>(PT); Fibroscan measurements, clinical significant changes in physical<br /><br>examination and/or reported physical complaints as assessed by the<br /><br>investigator.</p><br>