TY - JOUR
T1 - Daclatasvir and sofosbuvir with ribavirin for 24 weeks in chronic hepatitis C genotype-3-infected patients with cirrhosis
T2 - A Phase III study (ALLY-3C)
AU - the ALLY-3C study team
AU - Poordad, Fred
AU - Shiffman, Mitchell L.
AU - Ghesquiere, Wayne
AU - Wong, Alexander
AU - Huhn, Gregory D.
AU - Wong, Florence
AU - Ramji, Alnoor
AU - Shafran, Stephen D.
AU - McPhee, Fiona
AU - Yang, Rong
AU - Noviello, Stephanie
AU - Linaberry, Misti
N1 - Funding Information:
FP reports grant support, speaker fees and advisory board honorarium from Bristol-Myers Squibb. MLS reports grant support, speaker fees and advisory board honorarium from AbbVie, Bristol-Myers Squibb, Gilead, Intercept and Merck; grant support from Conatus, CymaBay, Exalenz, Galectin, Genfit, Immuron, NGM Biopharmaceuticals, Novartis and Shire; speaker fees from Bayer and Daiichi Sankyo; consulting fees from OptumRx. AW reports grant support, personal fees and non-financial support from Gilead; grant support and personal fees from AbbVie and Merck; personal fees from Bristol-Myers Squibb. GDH reports grant support from Bristol-Myers Squibb along with grant support, personal fees and consulting fees from Gilead during the conduct of the study; grant support, personal fees and consulting fees from Janssen, grant support and personal fees from ViiV, personal fees from Theratechnologies, grant support from Proteus outside of the submitted work. AR reports grant support and personal fees from AbbVie, Gilead and Merck; personal fees from Bristol-Myers Squibb, Celgene, Allergan, Janssen, Intercept, Lupin and Novartis. SDS reports grant support during the conduct of the study; grant support from AbbVie and Janssen, grant support and personal fees from Gilead and Merck, personal fees from Pfizer outside of the submitted work. FM is an employee of Bristol-Myers Squibb. RY is an employee and stockholder of Bristol-Myers Squibb. SN is an employee and stockholder of Bristol-Myers Squibb; stockholder of Merck/Schering-Plough and Johnson & Johnson. ML is an employee of Bristol-Myers Squibb. The remaining authors declare no competing interests.
Funding Information:
This study was funded by Bristol-Myers Squibb. The authors would like to thank Eugene Scott Swenson, a BMS employee at the time that ALLY-3C was planned and undertaken, for his assistance with developing the study protocol and initiating the study. Editorial assistance with the manuscript was provided by Nick Fitch of Articulate Science (London, UK) and funded by Bristol-Myers Squibb.
Publisher Copyright:
©2019 International Medical Press.
PY - 2019
Y1 - 2019
N2 - Background: Optimal treatment for patients with HCV genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. Methods: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary end point was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks’ daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% CI lower bound >79.0%). Results: A total of 78 patients were treated (54 treatment-naive, 24 treatment-experienced including 8 with prior sofosbuvir exposure). SVR12 was achieved by 87% (68/78; 95% CI 77.7, 93.7%) of patients in the primary analysis of central laboratory data. One additional patient achieved SVR12 by local testing resulting in an overall SVR12 rate of 88% (95% CI 79.2, 94.6%) and the lower bound of the 95% CI above the historical threshold. SVR12 rates were 93% (50/54) for treatment-naive and 79% (19/24) for treatment-experienced patients. Of the nine non-SVR12 patients, four were lost to follow-up, two relapsed (both sofosbuvir-experienced), two had end-of-treatment virological failure and one discontinued early. There were no unexpected safety signals; only one patient discontinued for an adverse event. Conclusions: Daclatasvir+sofosbuvir+ribavirin for 24 weeks was well tolerated and efficacious in HCV genotype-3-infected patients with compensated cirrhosis, with SVR12 outcomes comparable to previously reported outcomes in patients treated with this regimen for 12–16 weeks. ClinicalTrials.gov ID NCT02673489.
AB - Background: Optimal treatment for patients with HCV genotype-3 infection and liver cirrhosis remains a medical priority. Daclatasvir+sofosbuvir and ribavirin is a recommended option for such patients, but clinical trial data are lacking for treatment >16 weeks. Methods: This was a single-arm, Phase III study of daclatasvir+sofosbuvir+ribavirin for 24 weeks in patients with compensated cirrhosis and HCV genotype-3 infection. The primary end point was sustained virological response at post-treatment week 12 (SVR12); the primary objective was to demonstrate statistical superiority to historical SVR12 data for 12 weeks’ daclatasvir+sofosbuvir without ribavirin in genotype-3-infected patients with cirrhosis (95% CI lower bound >79.0%). Results: A total of 78 patients were treated (54 treatment-naive, 24 treatment-experienced including 8 with prior sofosbuvir exposure). SVR12 was achieved by 87% (68/78; 95% CI 77.7, 93.7%) of patients in the primary analysis of central laboratory data. One additional patient achieved SVR12 by local testing resulting in an overall SVR12 rate of 88% (95% CI 79.2, 94.6%) and the lower bound of the 95% CI above the historical threshold. SVR12 rates were 93% (50/54) for treatment-naive and 79% (19/24) for treatment-experienced patients. Of the nine non-SVR12 patients, four were lost to follow-up, two relapsed (both sofosbuvir-experienced), two had end-of-treatment virological failure and one discontinued early. There were no unexpected safety signals; only one patient discontinued for an adverse event. Conclusions: Daclatasvir+sofosbuvir+ribavirin for 24 weeks was well tolerated and efficacious in HCV genotype-3-infected patients with compensated cirrhosis, with SVR12 outcomes comparable to previously reported outcomes in patients treated with this regimen for 12–16 weeks. ClinicalTrials.gov ID NCT02673489.
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U2 - 10.3851/IMP3278
DO - 10.3851/IMP3278
M3 - Article
C2 - 30382942
AN - SCOPUS:85064220348
VL - 24
SP - 35
EP - 44
JO - Antiviral Therapy
JF - Antiviral Therapy
SN - 1359-6535
IS - 1
ER -