i
A Randomized, Proof-of-Concept Clinical Trial on Repurposing Chlorcyclizine for the Treatment of Chronic Hepatitis C
-
3 2019
-
-
Source: Antiviral Res. 163:149-155
[PDF-1.10 MB]
Details:
-
Alternative Title:Antiviral Res
-
Personal Author:
-
Description:Background & Aims:
Chlorcyclizine HCl (CCZ) is a piperazine-class antihistamine with anti-hepatitis C virus (HCV) activity in vitro and in vivo. In a first-in-humans study for HCV, we evaluated the antiviral effects and safety of CCZ±ribavirin (RBV), characterized pharmacokinetic (PK) and viral kinetic (VK) patterns, and provide insights into CCZs mode of action against HCV.
Methods:
Chronic HCV patients were randomized to CCZ (75mg twice daily) or CCZ+weight-based RBV (1000/1200mg daily) for 28 days. Therapy started with a loading dose of CCZ 150mg±RBV. Serial assessments of safety, liver tests, PK and VK markers were obtained.
Results:
24 HCV patients were treated; 54% male, median age 56 years, median HCV RNA 6.30 log IU/ml, without baseline differences between groups. At the end of therapy, subjects treated with CCZ monotherapy did not show any significant or sustained reduction in viremia (p=0.69), whereas 7/12 (58%) subjects treated with CCZ+RBV had a >3-fold decline in HCV RNA. Subjects who responded demonstrated monophasic (n=2), biphasic (n=2) and triphasic (n=3) VK responses. Contrary to historical RBV monotherapy response, CCZ+RBV demonstrated a continued viral decline suggesting a possible synergistic effect of CCZ+RBV. Mathematical modeling predicts a median effectiveness of CCZ+RBV in blocking viral production (ε) of 59% (Interquartile range, IQR: 50%) and blocking infection (η) of 78% (IQR: 23%). Adverse events (AEs) were mild-moderate without treatment discontinuations for AEs.
Conclusions:
In this human pilot study, CCZ demonstrated some anti-HCV effects, mostly in combination with RBV. More potent CCZ derivatives with optimal PK features may be more suitable for future therapeutic development. ClinicalTrials.gov number: NCT02118012
-
Keywords:
-
Source:
-
Pubmed ID:30711416
-
Pubmed Central ID:PMC6402797
-
Document Type:
-
Funding:
-
Collection(s):
-
Main Document Checksum:
-
Download URL:
-
File Type:
