Inferior cure rate in pilot study of 4‐week glecaprevir/pibrentasvir treatment with or without ribavirin of chronic hepatitis C

Abstract

Background & Aims Shortening the treatment duration for chronic hepatitis C may increase feasibility and reduce the cost of cure. The aims of this study were to compare 4 weeks of glecaprevir/pibrentasvir (GLE/PIB) treatment with and without ribavirin for patients with chronic hepatitis C and favourable baseline characteristics and to monitor the development of resistance‐associated substitutions (RAS) and re‐treatment outcomes if treatment failed. Methods We performed an open‐label single‐centre randomized controlled trial, in which patients with chronic hepatitis C were randomized 1:1 to GLE/PIB ± ribavirin, stratified by genotype 3. The main inclusion criteria were treatment‐naive patients, aged 18‐49 with all genotypes accepted, and absence of liver fibrosis, determined by liver stiffness measurement less than 8 kPa. Viral genome sequences were determined by deep sequencing at baseline and at the time of relapse. Results A total of 32 patients started treatment. Sustained virological response at week 12 (SVR12) was 59% (10/17) for GLE/PIB without ribavirin and 73% (11/15) for GLE/PIB with ribavirin. Drug target‐specific NS5A RAS were detected at baseline for 45% (5/11) of patients with treatment failure and for 14% (3/21) of patients who achieved SVR12. Ten failure patients were retreated 12 weeks with sofosbuvir‐based regimens; all have been cured. Conclusions In this pilot study of 4‐week treatment with GLE/PIB with and without ribavirin, we found that baseline RAS were more frequent in patients with virological failure. Development of RAS did occur after short treatment but did not result in retreatment failure with a different regimen. EudraCT no: 2017‐005179‐21.

Four Weeks Treatment with Glecaprevir/Pibrentasvir + Ribavirin—A Randomized Controlled Clinical Trial

“…The reason why viral load was not included in this study design is that we wanted a simple and replicable design that easily could be transferred to clinical practice and especially in resource limited areas where preclinical baseline variables can be difficult to obtain. In addition, baseline viral load was not found to be a predictor of achieving SVR12 in the first phase of the study [ 19 ]. Another approach to reduce treatment duration is response-guided therapy.…”

“…A REDCAP database served as the electronic case report form (e-CRF) where all clinical data were recorded. Initially patients were seen eight times during the 48-week study period with blood samples at each visit as in the first phase of the study [ 19 ]; see Supplemental Table S1 . An amendment changed this in January 2020 so patients should only be physically present at the first three visits (screening, treatment start and two weeks after treatment start).…”

“…So far, the clinical trials of ultra-short treatment of four weeks or less have overall been disappointing and characterized by a low number of participants [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The 4RIBC study was designed in two phases where the aim of the first phase was to evaluate if four weeks’ treatment with glecaprevir/pibrentasvir (GLE/PIB) without ribavirin would be feasible [ 19 ]. It showed a cure rate of 73% after four weeks’ treatment with GLE/PIB + ribavirin, and 59% without ribavirin.…”

Soluble inflammatory mediators identify HCV patients who may be cured with four weeks of antiviral treatment

“…Study details have recently been reported. 8 In total, 17 received GLE/PIB and 15 patients received GLE/PIB plus ribavirin. Overall, 21 patients achieved SVR and 11 experienced treatment failure.…”

Characterization of a Novel Hepatitis C Virus Genotype 1 Subtype from a Patient Failing 4 Weeks of Glecaprevir-Pibrentasvir Treatment

“…HCV is divided into 8 genotypes and >90 subtypes, and unassigned putative subtypes are still being detected, e.g., in Africa ( 2 – 4 ). By deep sequencing, we investigated an unknown subtype of HCV genotype 1 from a patient participating in the 4RIBC study ( 5 ) (EudraCT no. 2017-005179-21) who had been treated for 4 weeks with glecaprevir and pibrentasvir (Maviret).…”