Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

Šperl, Jan; Horváth, Gábor; Halota, Waldemar; Ruiz-Tapiador, Juan Arenas; Streinu-Cercel, Adrian; Jančorienė, Ligita; Werling, Klára; Kileng, Hege; Köklü, Seyfettin; Gerstoft, Jan; Urbánek, Petr; Flisiak, Robert; Leiva, Rafael Alexander; Kazėnaitė, Edita; Prinzing, R.; Patel, Sushma; Qiu, Jingjun; Asante‐Appiah, Ernest; Nguyen, Bach‐Yen; Barr, Eliav; Platt, Heather

doi:10.1016/j.jhep.2016.07.050

Cited by 49 publications

(39 citation statements)

References 20 publications

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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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“…Overall, six trials with 2346 patients fulfilled the inclusion criteria ( Figure 1) [20][21][22][23][24][25] . A total 1625 patients were treated with sofosbuvir, either alone or in combination with other agents, such as ribarivin ± peginterferon (57%), velpatasvir (38%) or ledispavir (5%).…”

Section: Included Trialsmentioning

confidence: 99%

“…a priori an open-label design 21,25 , while in the VALENCE study 22 randomization codes were revealed to terminate with the placebo arm due to the efficacy data reported in the FISSION trial 21 . In these trials the report of any adverse events could be done unblinded.…”

Section: Risk Of Biasmentioning

confidence: 99%

Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

et al. 2017

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“…This is a post hoc, integrated analysis of data from 11 clinical trials in the EBR/GZR phase 2/3 clinical development program. The 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‐Inherited Blood Disorders [NCT02252016/Protocol PN065]; and C‐CORAL [NCT02251990/Protocol PN067]). The C‐SALT [NCT02115321/Protocol PN059] study has not been published in full.…”

Section: Methodsmentioning

confidence: 99%

The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: An integrated analysis

Serfaty

Jacobson

Rockstroh

et al. 2019

Journal of Viral Hepatitis

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Summary European treatment guidelines for hepatitis C virus (HCV) infection recommend that people with genotype (GT) 1a infection and baseline viral load ≤800 000 IU/mL receive elbasvir/grazoprevir (EBR/GZR) for 12 weeks, and those with baseline viral load >800 000 IU/mL receive EBR/GZR plus ribavirin for 16 weeks. This analysis was conducted to clarify whether baseline viral load can serve as an accurate, sensitive or specific stratification factor for defining EBR/GZR regimens. In this post hoc, integrated analysis, participants with GT1a infection who received EBR 50 mg/GZR 100 mg for 12 weeks were stratified according to baseline viral load. Sustained virologic response at 12 weeks post‐treatment was achieved by 95.2% (911/957) of participants and was higher among participants with baseline viral load ≤800 000 IU/mL vs >800 000 IU/mL (98.5% vs 93.9%). The 800 000 IU/mL threshold had a positive predictive value of 98.5%, a negative predictive value of 6.1%, a specificity of 91.3%, a sensitivity of 28.4% and an overall accuracy of 31.5%. A baseline viral load cutpoint of 800 000 IU/mL had high positive predictive value and specificity but poor negative predictive value, sensitivity and accuracy in predicting treatment outcomes in this population. Baseline NS5A resistance‐associated substitutions (RASs) were detected in 25% (1/4) of virologic failures with baseline viral load ≤800 000 IU/mL and 59.5% (25/42) of those with baseline viral load >800 000 IU/mL. Overall, these data suggest that, compared with the use of a baseline viral load cutpoint, baseline testing for NS5A RASs enables more individuals to receive the 12‐week EBR/GZR regimen without compromising the opportunity for SVR.

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Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

Cited by 49 publications

References 20 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

Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis

The accuracy of baseline viral load for predicting the efficacy of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1a infection: An integrated analysis

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