Original ResearchFull Report: Clinical—LiverDaclatasvir Plus Peginterferon and Ribavirin Is Noninferior to Peginterferon and Ribavirin Alone, and Reduces the Duration of Treatment for HCV Genotype 2 or 3 Infection
Section snippets
Study Design
The objective of this randomized, double-blind, 3-arm phase 2b study was to compare the antiviral activity and safety of 12 or 16 weeks of treatment with daclatasvir plus peg-alfa/RBV with 24 weeks of treatment with placebo plus peg-alfa-2a/RBV (Supplementary Figure 1) (study AI444-031; clinicaltrials.gov identifier NCT01257204). Patients on daclatasvir-containing regimens who achieved a protocol-defined response (PDR) (HCV-RNA level < lower limit of quantitation [LLOQ] at week 4 and < LLOQ
Patients
A total of 196 patients were screened; 152 were assigned randomly to treatment groups and 151 were treated (Figure 1). Forty-four patients were not randomized; the predominant reason was that these patients no longer met the study protocol entry criteria. One patient (in the daclatasvir 16-week group) was randomized but withdrew consent before initiating study treatment and was excluded from the modified intention-to-treat population for subsequent analyses. Study treatment was completed by 131
Discussion
Therapeutic regimens that include direct-acting antivirals can increase efficacy and reduce the required duration of therapy for patients with chronic HCV infection, providing advantages for both patients and health care providers. Results of this study confirm that the pan-genotypic in vitro activity of daclatasvir is reflected by clinical activity in patients infected with genotypes 2 and 3, consistent with previous data in patients infected with genotypes 1 and 4.12, 16, 17 Addition of
Acknowledgments
The authors thank the patients and their families, research staff at all participating sites, and Bristol-Myers Squibb Research and Development colleagues.
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Hepatitis C
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2018, Drug Resistance UpdatesIdentification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus Genotype 3 Infection: A Systematic Review and Network Meta-analysis
2017, Clinical Gastroenterology and HepatologyDaclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin
2016, International Journal of Infectious DiseasesCitation Excerpt :On the other hand, sub-optimal drug levels allow the selection of RAVs and fail to contribute to antiviral activity, as seen in patient 6. However, other factors need to be taken into account, such as the baseline HCV plasma level, body mass index, interleukin 28 (IL28) genotype, and co-administered drug activity.7 The HAART regimen of patient 6 was compatible with the anti-HCV therapy and no other drug with possible known interactions was co-administered,8,9 so no definite reason for his low DCV level was found.
New Direct-Acting Antivirals for the Treatment of Patients With Hepatitis C Virus Infection: A Systematic Review of Randomized Controlled Trials
2019, Journal of Clinical and Experimental HepatologyCitation Excerpt :We excluded 70 studies because they (i) evaluated IFN-free DAA regimens (n = 16); (ii) compared DAA regimens with or without RBV (n = 8); (iii) did not test DAAs (n = 3); (iv) were not RCTs (n = 7); (v) compared different regimens of the same DAAs (i.e. all patients took the experimental drug, n = 11); (vi) tested DAAs that were administered for only few days (n = 12); (vii) did not report data on SVR rate (n = 7); (viii) were review articles (n = 4); and (ix) included patients after liver transplantation or HIV coinfection (n = 2) (Supplementary Table II reports the list of excluded trials). Finally, we included 28 trials26–53 enrolling 7710 patients (Figure 1). The search in clinicaltrials.gov revealed 15 ongoing studies (last update May 2017) that met the inclusion criteria.
Conflicts of interest These authors disclose the following: Gregory Dore has been a clinical investigator, consultant, speaker, and/or has received travel sponsorship from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche, and Vertex; Eric Lawitz has been a consultant, research grant recipient, and/or speaker for AbbVie, Achillion, BioCryst, Biotica, Boehringer Ingelheim, Bristol-Myers Squibb, Enanta, Gilead, GlaxoSmithKline, Idenix, Intercept, Janssen, Kadmon, Medtronic, Merck, Novartis, Presidio, Roche, Santaris, Theravance, and Vertex; Christophe Hézode has been a clinical investigator, speaker, and/or consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Roche; Stephen Shafran has been a clinical investigator, speaker, and/or consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, Pfizer, Roche, and Vertex; Alnoor Ramji has been a clinical investigator, consultant, speaker, and/or received research grants from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck, Roche, Vertex, Janssen, and Novartis; Harvey Tatum has been a clinical investigator and/or speaker for Gilead, Merck, AbbVie, Boehringer Ingelheim, and Genentech; Gloria Taliani has received personal fees from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Roche; Albert Tran has been a clinical investigator for AbbVie, Bristol-Myers Squibb, Gilead, and Janssen; Maurizia Brunetto has received personal fees from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck, Novartis, and Roche; Simone Strasser has been a consultant, speaker, and has received travel support from Bristol-Myers Squibb; Nina Weis has been a clinical investigator, consultant, and/or speaker for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, and Roche; Samuel Lee has received research grants and personal fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche, and Vertex; Dominique Larrey has been a consultant and/or clinical investigator for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche, and Sanofi; Hugh Harley has been a consultant for Bristol-Myers Squibb; Jacob George has been a consultant and has received lecture fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, and Roche; Scott Fung has been a speaker/consultant for Gilead, Merck, Roche, and Vertex; Victor de Lédinghen has received personal fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Echosens, Gilead, Janssen, Merck, and Roche; Peggy Hagens, Fiona McPhee, Dennis Hernandez, David Cohen, Elizabeth Cooney, Stephanie Noviello, and Eric Hughes are employees of Bristol-Myers Squibb. The remaining authors disclose no conflicts.
Funding This study was funded by Bristol-Myers Squibb; the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney (J.G.); and a National Health and Medical Research Council of Australia program grant (1053206) and project grant (1047417). Bristol-Myers Squibb also provided funding for the editorial assistance services of Richard Boehme, PhD, of Articulate Science, for the preparation of this manuscript.