Dataset Information

The efficacy of Elbasvir/Grazoprevir fixed-dose combination for 8 weeks in HCV treatment and health-related quality of life (HRQoL) in treatment-naive, non-cirrhotic, genotype 4-infected patients (ELEGANT-4): A single-center, single-arm, open-label, phase 3 trial.

ABSTRACT:

Background

Cost, adverse events, and long treatment duration can be significant obstacles in treating hepatitis C virus (HCV)-infected individuals. Shortening the treatment regimen can minimize these barriers, thereby enhancing adherence and increasing medication availability to more patients.

Methods

This is a single-centre, single-arm, open-label, phase 3 clinical trial on treatment naïve, non-cirrhotic, HCV genotype 4 patients. The study aimed to evaluate an 8-week course of Elbasvir (ELB)/Grazoprevir (GZR) in this population. The primary endpoint was sustained virologic response at 12 weeks after the end of treatment (SVR-12). The secondary endpoints were SVR-4, adverse events, and changes in health- and hepatitis-related quality of life (HRQoL).

Results

Of the 30 patients who were enrolled, 29 (97%) achieved SVR-12 and SVR-4 (95% CI: 90-100%). No patients experienced serious or life-threatening adverse events (AEs), but mild/moderate AEs were reported by 16 (53%). The most commonly reported AEs were itching/skin rash (20%), headache (16.7%), abdominal/epigastric pain and decreased appetite (13.3% each), and nausea/vomiting (10%). Marked improvements in HRQoL were reported between the first (baseline) and third (SVR-12) timepoints. HRQoL score improvements involved the physical, mental, and hepatitis-specific indices, and ranged between 6 and 42 points (out of 100, P ≤0.003).

Conclusion

The trial provides empirical evidence that HCV genotype 4-infected patients can achieve viral eradication with an 8-week-regimen of ELB/GZR. Further, this course of treatment is associated with a minimal adverse event profile and potentially significant improvements in quality of life. (ClinicalTrials.gov number, NCT03578640).

SUBMITTER: AlEid A

PROVIDER: S-EPMC9212120 | biostudies-literature | 2022 May-Jun

REPOSITORIES: biostudies-literature

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Publications

The efficacy of Elbasvir/Grazoprevir fixed-dose combination for 8 weeks in HCV treatment and health-related quality of life (HRQoL) in treatment-naïve, non-cirrhotic, genotype 4-infected patients (ELEGANT-4): A single-center, single-arm, open-label, phase 3 trial.

AlEid Ahmad A Al Balkhi Areej A Qutub Adel A Abbarh Shahem S AlLehibi Abed A Almtawa Abdullah A Al Otaibi Nawwaf N AlGhamdi Ahmed A AlGhamdi Adel A Alamr Abdulrahman A Ahmad Shameem S Al Sayari Khalid K Al Ibrahim Bashaar B AlKhathlan Abdullah A

Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association 20220501 3

<h4>Background</h4>Cost, adverse events, and long treatment duration can be significant obstacles in treating hepatitis C virus (HCV)-infected individuals. Shortening the treatment regimen can minimize these barriers, thereby enhancing adherence and increasing medication availability to more patients.<h4>Methods</h4>This is a single-centre, single-arm, open-label, phase 3 clinical trial on treatment naïve, non-cirrhotic, HCV genotype 4 patients. The study aimed to evaluate an 8-week course of El ...[more]

PMID: 35142658

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Project description:ObjectiveThis study aims to systematically review recent economic evaluations of elbasvir/grazoprevir (EBR/GZR) for chronic hepatitis C (CHC), to critically appraise the reporting quality and to summarize the results.MethodsA literature search was undertaken using Medline, Embase, the Cochrane Library, EconLit, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP to identify original articles containing economic evaluations of EBR/GZR for CHC published between 1 January 2000 and 31 December 2020. The Consolidated Health Economic Evaluation Reporting Standards statement was used to assess the quality of reporting of the articles.ResultsOf 93 articles identified, 13 studies fulfilled the inclusion criteria. These studies were conducted in 4 countries, and 8 active interventions were assessed. The target population was patients infected with CHC genotype 1 infection in all studies. Eight out of 13 studies that compared EBR/GZR vs. other direct antiviral agents suggested that EBR/GZR was generally more cost-effective or dominant than daclatasvir/asunaprevir (DCV/ASV), sofosbuvir/velpatasvir (SOF/VEL), ledipasvir/sofosbuvir (LDV/SOF), ombitasvir/paritaprevir/ritonavir + dasabuvir (3D) but not more cost-effective than glecaprevir/pibrentasvir (GLE/PIB). Two studies from China and one study from the USA that compared EBR/GZR vs. pegylated interferon and ribavirin (PegIFN/RBV) consistently indicated that EBR/GZR was generally more cost-effective than PegIFN/RBV. One study from Italy compared EBR/GZR with SOF + PegIFN/RBV and suggested that EBR/GZR had a lower cost and higher effectiveness. One study from France and one study from the USA confirmed that compared with non-therapy for patients with chronic kidney disease, EBR/GZR was cost-effective at commonly accepted current standards. All included studies were of good quality of reporting, with an average score of 21.9 (range 19-23).ConclusionEBR/GZR for CHC genotype 1 might be cost-effective or dominant compared with PegIFN/RBV and other direct antiviral agents (SOF/VEL, 3D, DCV/ASV, LDF/SOF) or non-therapy. However, under certain assumptions, EBR/GZR was not a cost-effective alternative for CHC patients vs. GLE/PIB.

Project description:The selection of resistance-associated variants (RAVs) against single agents administered to patients chronically infected with hepatitis C virus (HCV) necessitates that direct-acting antiviral agents (DAAs) targeting multiple viral proteins be developed to overcome failure resulting from emergence of resistance. The combination of grazoprevir (formerly MK-5172), an NS3/4A protease inhibitor, and elbasvir (formerly MK-8742), an NS5A inhibitor, was therefore studied in genotype 1a (GT1a) replicon cells. Both compounds were independently highly potent in GT1a wild-type replicon cells, with 90% effective concentration (EC90) values of 0.9 nM and 0.006 nM for grazoprevir and elbasvir, respectively. No cross-resistance was observed when clinically relevant NS5A and NS3 RAVs were profiled against grazoprevir and elbasvir, respectively. Kinetic analyses of HCV RNA reduction over 14 days showed that grazoprevir and elbasvir inhibited prototypic NS5A Y93H and NS3 R155K RAVs, respectively, with kinetics comparable to those for the wild-type GT1a replicon. In combination, grazoprevir and elbasvir interacted additively in GT1a replicon cells. Colony formation assays with a 10-fold multiple of the EC90 values of the grazoprevir-elbasvir inhibitor combination suppressed emergence of resistant colonies, compared to a 100-fold multiple for the independent agents. The selected resistant colonies with the combination harbored RAVs that required two or more nucleotide changes in the codons. Mutations in the cognate gene caused greater potency losses for elbasvir than for grazoprevir. Replicons bearing RAVs identified from resistant colonies showed reduced fitness for several cell lines and may contribute to the activity of the combination. These studies demonstrate that the combination of grazoprevir and elbasvir exerts a potent effect on HCV RNA replication and presents a high genetic barrier to resistance. The combination of grazoprevir and elbasvir is currently approved for chronic HCV infection.