Maria Buti1, Kosh Agarwal2, Yves Horsmans3, William Sievert4, Ewa Janczewska5, Stefan Zeuzem6, Lisa Nyberg7, Robert S Brown8, Christophe Hézode9, Mario Rizzetto10, Raymundo Paraná11, Sandra De Meyer12, Ralph De Masi13, Donghan Luo13, Kirk Bertelsen13, James Witek13. 1. Liver Unit, Department of Internal Medicine, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain. Electronic address: mbuti@vhebron.net. 2. Institute of Liver Studies, Kings College Hospital, London, England. 3. Clinical Pharmacology Unit, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. 4. Gastroenterology and Hepatology Unit, Monash Medical Centre and Monash University, Melbourne, Australia. 5. Outpatients Clinic for Hepatology, Outpatients Clinic for Hepatology, ID Clinic, Myslowice, Poland. 6. Department of Medicine I, Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. 7. Hepatology Research Department, Kaiser Permanente, San Diego, California. 8. Department of Hepatology and Gastroenterology, Columbia University College of Physicians and Surgeons, New York, New York. 9. Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Créteil, France. 10. Department of Hepatology and Gastroenterology, University of Torino, Torino, Italy. 11. Gastro-Hepatology Unit, Medical School, Federal University of Bahia, Bahia, Brazil. 12. Janssen Infectious Diseases BVBA, Beerse, Belgium. 13. Janssen Research & Development LLC, Titusville, New Jersey.
Abstract
BACKGROUND & AIMS: We performed an open-label, multicenter, phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis. METHODS: Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25 IU/mL or for 36 weeks if their level was higher. The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups). RESULTS: At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who were treated with telaprevir twice daily, 74.3% achieved SVR12 compared with 72.8% of patients who were treated with telaprevir every 8 hours (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12. The most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours. CONCLUSIONS: Based on a phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov, Number: NCT01241760.
RCT Entities:
BACKGROUND & AIMS: We performed an open-label, multicenter, phase 3 study of the safety and efficacy of twice-daily telaprevir in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 1 infection, including those with cirrhosis. METHODS:Patients were randomly assigned to groups treated with telaprevir 1125 mg twice daily or 750 mg every 8 hours plus peginterferon alfa-2a and ribavirin for 12 weeks; patients were then treated with peginterferon alfa-2a and ribavirin alone for 12 weeks if their level of HCV RNA at week 4 was <25 IU/mL or for 36 weeks if their level was higher. The primary objective was to demonstrate noninferiority of telaprevir twice daily versus every 8 hours in producing a sustained virological response 12 weeks after the end of therapy (SVR12) (based on a -11% lower limit of the 95% lower confidence interval for the difference between groups). RESULTS: At baseline, of 740 patients, 85% had levels of HCV RNA ≥800,000 IU/mL, 28% had fibrosis (F3-F4), 14% had cirrhosis (F4), 57% were infected with HCV genotype 1a, and 71% had the non-CC IL28B genotype. Of patients who were treated with telaprevir twice daily, 74.3% achieved SVR12 compared with 72.8% of patients who were treated with telaprevir every 8 hours (difference in response, 1.5%; 95% confidence interval, -4.9% to 12.0%), so telaprevir twice daily is noninferior to telaprevir every 8 hours. All subgroups of patients who were treated with telaprevir twice daily versus those who were treated every 8 hours had similar rates of SVR12. The most frequent adverse events (AEs) in the telaprevir phase were fatigue (47%), pruritus (43%), anemia (42%), nausea (37%), rash (35%), and headache (26%); serious AEs were reported in 9% of patients. Rates of AEs and serious AEs were similar or slightly higher among patients treated with telaprevir every 8 hours. CONCLUSIONS: Based on a phase 3 trial, telaprevir twice daily is noninferior to every 8 hours in producing SVR12, with similar levels of safety and tolerability. These results support use of telaprevir twice daily in patients with chronic HCV genotype 1 infection, including those with cirrhosis. ClinicalTrials.gov, Number: NCT01241760.
Authors: Alain H Litwin; Irene J Soloway; Lauren Cockerham-Colas; Sheila Reynoso; Moonseong Heo; Christopher Tenore; Robert J Roose Journal: Int J Drug Policy Date: 2015-08-20