Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study - 29/10/16

Doi : 10.1016/S1473-3099(16)30408-X

Katja Deterding, MD ^a,^c, Christoph D Spinner, MD ^d, Eckart Schott, ProfMD ^e, Tania M Welzel, MD ^f, Guido Gerken, ProfMD ^g, Hartwig Klinker, ProfMD ^h, Ulrich Spengler, ProfMD ⁱ, Johannes Wiegand, MD ^j, Julian Schulze zur Wiesch, MD ^k, Anita Pathil, MD ^l, Markus Cornberg, ProfMD ^a,^c,^m, Andreas Umgelter, MD ^d, Caroline Zöllner, MD ^e, Stefan Zeuzem, ProfMD ^f, Armin Papkalla, PhD ⁿ, Kristina Weber, PhD ^b, Svenja Hardtke, PhD ^c,^m, Heiko von der Leyen, ProfMD ⁿ, Armin Koch, ProfPhD ^b, Dorothee von Witzendorff, PhD ^c, Michael P Manns, ProfMD ^a,^c,^m,^⁎ , Heiner Wedemeyer, ProfMD ^a,^c,^m,^⁎
the
HepNet Acute HCV IV Study Group^{^†}
Members listed in the Supplementary Material

^a Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany

^b Department of Biostatistics, Hannover Medical School, Hannover, Germany

^c HepNet Study-House, German Liver Foundation, Hannover, Germany

^d Department of Medicine II, University Hospital Klinikum rechts der Isar, Munich, Germany

^e Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany

^f Department of Medicine, University Hospital Frankfurt, Frankfurt, Germany

^g Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany

^h Department of Internal Medicine II, Division of Infectious Diseases, University of Würzburg Medical Center, Würzburg, Germany

ⁱ Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany

^j Department of Gastroenterology and Rheumatology, Section of Hepatology, University of Leipzig, Leipzig, Germany

^k Department of Internal Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany

^l Department of Internal Medicine IV, Gastroenterology and Hepatology, University Clinic of Heidelberg, Heidelberg, Germany

^m German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Germany

ⁿ Hannover Clinical Trial Center, Hannover, Germany

^* Correspondence to: Prof Heiner Wedemeyer, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany Correspondence to: Prof Heiner Wedemeyer Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Hannover 30625 Germany ^** Prof Michael P Manns, Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany Prof Michael P Manns Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Hannover 30625 Germany

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Summary

Background

Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa is highly effective, but can be associated with frequent side-effects. We investigated the safety and efficacy of an interferon-free regimen for treatment of acute HCV infection.

Methods

In this prospective, open-label, multicentre, single-arm pilot study, we enrolled adults (≥18 years) with acute HCV genotype 1 monoinfection from ten centres in Germany. Patients were given ledipasvir (90 mg) plus sofosbuvir (400 mg) as a fixed-dose combination tablet once daily for 6 weeks. The primary efficacy outcome was the proportion of patients with sustained virological response (defined as undetectable HCV RNA 12 weeks after the end of treatment; other primary outcomes were safety and tolerability of ledipasvir plus sofosbuvir. The primary analysis population consisted of all patients who received at least one dose of study drug. Safety was also assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, number NCT02309918.

Findings

Between Nov 19, 2014, and Nov 10, 2015, we enrolled 20 patients. Median HCV RNA viral load at baseline was 4·04 log₁₀ IU/mL (1·71–7·20); 11 patients were infected with HCV genotype 1a and nine patients with genotype 1b. All patients achieved a sustained virological response 12 weeks after the end of treatment (20 [100%] of 20 patients). Treatment was well tolerated; there were no drug-related serious adverse events. Up to 12 weeks after treatment, 22 possible or probable drug-related adverse events were reported. There was one serious adverse event, which was judged unrelated to the study drug; one patient was admitted to hospital for surgery of a ruptured cruciate ligament.

Interpretation

Treatment for 6 weeks with ledipasvir plus sofosbuvir was well tolerated and highly effective in patients with acute HCV genotype 1 monoinfection. Short-duration treatment of acute hepatitis C might prevent the spread of HCV in high-risk populations.