Efficacy of 8 Weeks of Sofosbuvir, Velpatasvir, and Voxilaprevir in Patients With Chronic HCV Infection: 2 Phase 3 Randomized Trials

Autor: Catherine A.M. Stedman, Yanni Zhu, Sergio Borgia, Bernard Willems, Bal Raj Bhandari, Edward Gane, Kosh Agarwal, Jordan J. Feld, Evguenia S. Svarovskaia, Hadas Dvory-Sobol, Alexander J. Thompson, Gregory J. Dore, Graham R. Foster, Tarik Asselah, Diana M. Brainard, John G. McHutchison, Ronald Nahass, G. Mani Subramanian, Thomas Berg, Luisa M. Stamm, Ira M. Jacobson, Eric Lawitz, M. Davis, Stephen D. Shafran, Peter Ruane, Robert H. Hyland, Kimberly A. Workowski, Stuart K. Roberts, Brian L. Pearlman, Norbert Bräu
Rok vydání: 2017
Předmět:
0301 basic medicine
Cyclopropanes
Male
Aminoisobutyric Acids
Sofosbuvir
Sustained Virologic Response
Gastroenterology
law.invention
0302 clinical medicine
Randomized controlled trial
law
Aged
80 and over
Sulfonamides
virus diseases
Hepatitis C
Middle Aged
Pibrentasvir
030211 gastroenterology & hepatology
Drug Therapy
Combination
Female
medicine.drug
Adult
medicine.medical_specialty
Macrocyclic Compounds
Adolescent
Proline
Voxilaprevir
Lactams
Macrocyclic
Sofosbuvir/velpatasvir
Antiviral Agents
Heterocyclic Compounds
4 or More Rings
03 medical and health sciences
Young Adult
Leucine
Internal medicine
Quinoxalines
medicine
Humans
Adverse effect
Aged
Hepatology
business.industry
Glecaprevir
Hepatitis C
Chronic
medicine.disease
digestive system diseases
Surgery
030104 developmental biology
Carbamates
business
Zdroj: Gastroenterology. 153(1)
ISSN: 1528-0012
Popis: Background & Aims Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). Methods In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%. Results In POLARIS-2, 95% (95% confidence interval [CI], 93%–97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%–99%; difference in the stratum-adjusted Mantel–Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%–99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by patients receiving voxilaprevir. In both trials, the proportion of patients who discontinued treatment because of adverse events was low (range, 0%–1%). Conclusions In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir. ClinicalTrials.gov numbers: POLARIS-2, NCT02607800; and POLARIS-3, NCT02639338.
Databáze: OpenAIRE
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