A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C.


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.

Chronic HCV patients were randomized to CCZ (75 mg twice daily) or CCZ+weight-based RBV (1000/1200 mg daily) for 28 days. Therapy started with a loading dose of CCZ 150 mg ± RBV. Serial assessments of safety, liver tests, PK and VK markers were obtained.

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. number: NCT02118012.

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.

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