Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C‐SCAPE study

Brown, Ashley; Hézode, Christophe; Zuckerman, Eli; Foster, Graham R.; Zekry, Amany; Roberts, Stuart K.; Lahser, Frederick; Durkan, C.; Badshah, Cyrus; Zhang, B.; Robertson, Michael; Wahl, Janice; Barr, Eliav; Haber, Barbara

doi:10.1111/jvh.12801

Cited by 25 publications

(21 citation statements)

References 17 publications

(23 reference statements)

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“…All participants provided voluntary written informed consent before trial entry. The detailed methodology and primary outcomes from these studies have been published previously (C‐SURFER [NCT02092350/Protocol PN052]; C‐EDGE CO‐INFECTION [NCT02105662/Protocol PN061]; C‐EDGE [Treatment‐Naive] [NCT02105467/Protocol PN060]; C‐EDGE [Treatment‐Experienced] [NCT02105701/Protocol PN068]; C‐WORTHY [NCT01717326/Protocol PN035]; C‐EDGE CO‐STAR [NCT02105688/Protocol PN062]; C‐EDGE Head‐2‐Head [NCT02358044/Protocol PN077]; Japan phase 2/3 study [NCT02203149/Protocol PN058]; C‐EDGE‐IBLD [NCT02252016/Protocol PN065]; C‐SCAPE [NCT01932762/Protocol PN047]; and C‐CORAL [NCT02251990/Protocol PN067]). The C‐SALT (NCT02115321/Protocol PN059) study has not yet been published in full.…”

Section: Methodsmentioning

confidence: 99%

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection

Wei

Kumada

Perumalswami

et al. 2019

J of Gastro and Hepatol

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Background and Aim Estimates suggest that in Asia, more than 31 million individuals have hepatitis C virus infection. The present analysis was conducted to assess the efficacy and safety of elbasvir/grazoprevir in Asian participants enrolled in the elbasvir/grazoprevir phase 2/3 clinical trials. Methods This is an integrated analysis of data from 12 international phase 2/3 clinical trials. Asian participants with chronic hepatitis C virus genotype 1 or 4 infection who received elbasvir 50 mg/grazoprevir 100 mg once daily for 12 weeks or elbasvir/grazoprevir plus ribavirin for 16 weeks were included in this analysis. The primary end point was sustained virologic response at 12 weeks after completion of therapy (SVR12). Results Seven hundred eighty Asian participants from 15 countries were included in this analysis. SVR12 was achieved by 756/780 (96.9%) of all participants, including 748/772 (96.9%) of those who received elbasvir/grazoprevir for 12 weeks and 8/8 (100%) of those who received elbasvir/grazoprevir plus ribavirin for 16 weeks. In the genotype 1b‐infected population, the SVR12 rate was 691/709 (97.5%), and there was no impact of age, high baseline viral load, or presence of cirrhosis. The most frequently reported adverse events were nasopharyngitis (8.0%), upper respiratory tract infection (5.4%), and diarrhea (5.2%). Twenty participants receiving elbasvir/grazoprevir for 12 weeks reported a total of 25 serious adverse events, and 7 (0.9%) discontinued treatment because of an adverse event. Conclusion Elbasvir/grazoprevir administered for 12 weeks is an effective and generally well‐tolerated treatment option for Asian individuals with hepatitis C virus genotype 1b infection.

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Section: Methodsmentioning

confidence: 99%

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection

Wei

Kumada

Perumalswami

et al. 2019

J of Gastro and Hepatol

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“…Interferon-free HCV treatment options with DAAs have expanded from the earlier regimens of sofosbuvir (SOF) plus ribavirin (RBV) [ 12 , 13 ], SOF plus daclatasvir [ 14 ], SOF plus simeprevir [ 14 , 15 ], SOF/ledipasvir [ 16 – 18 ], ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) with or without dasabuvir [ 19 , 20 ], and elbasvir/grazoprevir [ 21 , 22 ]. Newer HCV treatment options include pan-genotypic regimens with shorter treatment duration and indications for difficult-to-treat patient populations [ 23 ], including glecaprevir/pibrentasvir [ 24 – 30 ], SOF/velpatasvir (VEL) [ 31 , 32 ], and SOF/VEL/voxilaprevir [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Hepatitis C virus genetic diversity by geographic region within genotype 1-6 subtypes among patients treated with glecaprevir and pibrentasvir

et al. 2018

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Hepatitis C virus (HCV) is genetically diverse and includes 7 genotypes and 67 confirmed subtypes, and the global distribution of each HCV genotype (GT) varies by geographic region. In this report, we utilized a large dataset of NS3/4A and NS5A sequences isolated from 2348 HCV GT1-6-infected patients treated with the regimen containing glecaprevir/pibrentasvir (GLE/PIB) to assess genetic diversity within HCV subtypes by geographic region using phylogenetic analyses, and evaluated the prevalence of baseline amino acid polymorphisms in NS3 and NS5A by region/country and phylogenetic cluster. Among 2348 NS3/4A and NS5A sequences, phylogenetic analysis identified 6 genotypes and 44 subtypes, including 3 GT1, 8 GT2, 3 GT3, 13 GT4, 1 GT5, and 16 GT6 subtypes. Phylogenetic analysis of HCV subtype 1a confirmed the presence of two clades, which differed by geographic region distribution and NS3 Q80K prevalence. We detected phylogenetic clustering by country in HCV subtypes 1a, 1b, 2a, 2b, and 5a, suggesting that genetically distinct virus lineages are circulating in different countries. In addition, two clades were detected in HCV GT4a and GT6e, and NS5A amino acid polymorphisms were differentially distributed between the 2 clades in each subtype. The prevalence of NS3 and NS5A baseline polymorphisms varied substantially by genotype and subtype; therefore, we also determined the activity of GLE or PIB against replicons containing NS3/4A or NS5A from HCV GT1-6 clinical samples representing 6 genotypes and 21 subtypes overall. GLE and PIB retained activity against the majority of HCV replicons containing NS3/4A or NS5A from HCV GT1-6 clinical samples, with a median EC50 of 0.29 nM for GLE and 1.1 pM for PIB in a transient replicon assay. The data presented in this report expands the available data on HCV epidemiology, subtype diversity by geographic region, and NS3 and NS5A baseline polymorphism prevalence.

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“…However, most HCV therapy studies have focused on the predominant genotypes in North America, eastern Asia, and Europe (GT-1 and GT-3). Recently, several DAA-based regimens have been evaluated in patients with a HCV GT-6 infection (15,16). In general, these DAA-based regimens have demonstrated high SVR in patients with an HCV GT-6 infection.…”

mentioning

confidence: 99%

Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on theIn VitroPotency of Direct-Acting Antiviral Agents

McPhee

Ueland

Vellucci

et al. 2019

Antimicrob Agents Chemother

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HCV genotype 6 (GT-6) is found predominantly in East and Southeast Asia. Clinical studies have focused on patients infected with hepatitis C virus (HCV) GT-6a, where high sustained virologic response (SVR) rates to direct-acting antivirals (DAAs) have been achieved. However, GT-6 is highly diverse, with 29 reported subtypes. We explored the diversity of GT-6 polymorphisms at residues associated with DAA resistance, their impact on DAA in vitro potency when evaluated in a GT-6a consensus replicon, and their association with specific GT-6 subtypes. GT-6 sequences from 25 patient-derived samples and 105 sequences from the U.S. HCV database were compared, and substitutions at resistance-associated residue positions were phenotyped against different DAAs. Preexisting resistance-associated substitutions (RASs) to NS3 protease (A156V and D168E) and NS5B nucleotide (L159F and S282C) inhibitors were rare (Ͻ4%). Preexisting RASs to NS5A inhibitors were common, especially at L28 (A/F/G/M/T/V) and R30 (E/N/S). In vitro susceptibilities of NS5A-L28A and -L28T were dramatically reduced against all tested NS5A drugs (90% effective concentration [EC 90 ] range, 119 to 2,032 nM) compared with susceptibilities against a GT-6a consensus replicon (EC 90 range, 0.1 to 19 nM). These L28 RASs preexisted in combination with R30S (EC 90 [L28A-R30S] of Ն720 nM or EC 90 [L28T-R30S] of Ն128 nM against tested DAAs) or as L28T-L31I (EC 90 [tested DAAs] of Ͼ5,000 nM) and were detected in evaluated GT-6b and -6f sequences. NS5A-L28A-R30A, observed in GT-6r, did not replicate. In conclusion, HCV GT-6b, GT-6f, and GT-6r sequences harbored highly resistant RASs to all evaluated NS5A drugs. Therefore, monitoring SVR in patients infected with these GT-6 subtypes treated with NS5A drug-containing regimens is suggested to confirm any association between noted NS5A polymorphisms and treatment failure.

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Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C‐SCAPE study

Cited by 25 publications

References 17 publications

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection

Safety and efficacy of elbasvir/grazoprevir in Asian participants with hepatitis C virus genotypes 1 and 4 infection

Hepatitis C virus genetic diversity by geographic region within genotype 1-6 subtypes among patients treated with glecaprevir and pibrentasvir

Impact of Preexisting Hepatitis C Virus Genotype 6 NS3, NS5A, and NS5B Polymorphisms on theIn VitroPotency of Direct-Acting Antiviral Agents

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