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Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.

ABSTRACT: Although direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA-containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical need. This phase 2, open-label study (MAGELLAN-1) evaluated the efficacy and safety of glecaprevir (GLE) + pibrentasvir (PIB) ± ribavirin (RBV) in HCV genotype 1-infected patients with prior virologic failure to HCV DAA-containing therapy. A total of 50 patients without cirrhosis were randomized to three arms: 200 mg GLE + 80 mg PIB (arm A), 300 mg GLE + 120 mg PIB with 800 mg once-daily RBV (arm B), or 300 mg GLE + 120 mg PIB without RBV (arm C). By intent-to-treat analysis, sustained virologic response at posttreatment week 12 was achieved in 100% (6/6, 95% confidence interval 61-100), 95% (21/22, 95% confidence interval 78-99), and 86% (19/22, 95% confidence interval 67-95) of patients in arms A, B, and C, respectively. Virologic failure occurred in no patients in arm A and in 1 patient each in arms B and C (two patients were lost to follow-up in arm C). The majority of adverse events were mild in severity; no serious adverse events related to study drug and no relevant laboratory abnormalities in alanine aminotransferase, total bilirubin, or hemoglobin were observed.

Conclusion

The combination of GLE and PIB was highly efficacious and well tolerated in patients with HCV genotype 1 infection and prior failure of DAA-containing therapy; RBV coadministration did not improve efficacy. (Hepatology 2017;66:389-397).

SUBMITTER: Poordad F

PROVIDER: S-EPMC5573922 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.

Poordad Fred F Felizarta Franco F Asatryan Armen A Sulkowski Mark S MS Reindollar Robert W RW Landis Charles S CS Gordon Stuart C SC Flamm Steven L SL Fried Michael W MW Bernstein David E DE Lin Chih-Wei CW Liu Ran R Lovell Sandra S SS Ng Teresa I TI Kort Jens J Mensa Federico J FJ

Hepatology (Baltimore, Md.) 20170410 2

Although direct-acting antiviral (DAA) therapies for chronic hepatitis C virus (HCV) infection have demonstrated high rates of sustained virologic response, virologic failure may still occur, potentially leading to the emergence of viral resistance, which can decrease the effectiveness of subsequent treatment. Treatment options for patients who failed previous DAA-containing regimens, particularly those with nonstructural protein 5A inhibitors, are limited and remain an area of unmet medical nee ...[more]

PMID: 28128852

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Project description:Background & aimsShort duration treatment may aid HCV elimination among key populations. This study evaluated the efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection.MethodsIn this single-arm multicentre international trial, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300 mg-120 mg daily for 4 weeks. Primary infection was defined as a first positive anti-HCV antibody and/or HCV RNA measurement within 6 months of enrolment and either acute clinical hepatitis within 12 months (symptomatic illness or alanine aminotransferase >10x the upper limit of normal) or antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within 6 months and prior clearance (spontaneous or treatment). The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) and per-protocol (PP) populations.ResultsTwenty-three participants (96% men, 70% HIV, 57% ever injected drugs) received treatment, of whom 74% had genotype 1a infection and 35% recent reinfection. At baseline, median duration of infection was 17 weeks (IQR 11-29) and HCV RNA was 5.8 log10IU/ml (IQR 5.2-6.9). SVR12 was achieved by 78% (18/23; 95% CI 56-93%) and 82% (18/22; 95% CI 60-95%) of the ITT and PP populations, respectively, and in 100% (12/12; 95% CI 74-100%) of participants with baseline HCV RNA ≤6 log10. There were four cases of virological failure (relapse); three received retreatment with 12 weeks sofosbuvir-velpatasvir or grazoprevir-elbasvir (SVR, n = 2; loss to follow-up, n = 1). No serious adverse events were reported.ConclusionWhile most achieved SVR, the efficacy of a 4-week regimen of glecaprevir-pibrentasvir was lower than observed with longer treatment durations (≥6 weeks) among people with recent HCV.Trial registrationClinicaltrials.gov Identifier: NCT02634008.Impact and implicationsShort duration treatment may aid HCV elimination among key populations. This investigator-initiated single-arm multicentre international pilot trial demonstrated that efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection was sub-optimal (SVR12 78% ITT, 82% PP). Baseline HCV RNA appeared to impact response, with higher efficacy among participants with lower baseline HCV RNA (≤6 log10; SVR12 100% ITT, 12/12). While most achieved SVR, the efficacy of 4 weeks of glecaprevir-pibrentasvir was below that seen with longer treatment durations (≥6 weeks).

Dataset Information

Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.

Conclusion

Publications

Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.

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