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Ledipasvir/Sofosbuvir-Based Treatment of Patients with Chronic Genotype-1 HCV Infection and Cirrhosis: Results from Two Phase II Studies
- Source :
- Antiviral Therapy. 21:679-687
- Publication Year :
- 2015
- Publisher :
- SAGE Publications, 2015.
-
Abstract
- Background Ledipasvir/sofosbuvir ± ribavirin administered for 12 weeks to patients with genotype-1 HCV infection and compensated cirrhosis is effective and well-tolerated. The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir/sofosbuvir plus the non-nucleotide NS5B inhibitor GS-9669 or the NS3/4A protease inhibitor vedroprevir could reduce treatment duration and/or eliminate the need for ribavirin in genotype-1 HCV-infected patients with compensated cirrhosis. Methods In TRILOGY-1, 100 cirrhotic patients were randomized (1:1:1) to 8 weeks of ledipasvir/sofosbuvir plus ribavirin, ledipasvir/sofosbuvir plus GS-9669 250 mg or ledipasvir/sofosbuvir plus GS-9669 500 mg. In TRIL-OGY-2, 46 previously treated cirrhotic patients were randomized (1:1) to 8 weeks of ledipasvir/sofosbuvir plus vedroprevir ± ribavirin. The primary end points were the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12) and safety. Results In both studies, most patients were male (each 65%) and white (92–96%), infected with HCV genotype-1a (62–70%) and had IL28B non-CC genotypes (82–87%). In total, 37–39% of patients were Hispanic or Latino. SVR12 rates were similar across treatment arms in TRIL-OGY-1 (82–91%) and TRILOGY-2 (88–95%); no patient had on-treatment virological failure. Two serious adverse events (acute myocardial infarction and cardiomyopathy) were reported in two patients participating in TRILOGY-1, both of whom had pre-existing cardiac conditions. Laboratory abnormalities were infrequent. Conclusions All ledipasvir/sofosbuvir-based regimens were well-tolerated. To shorten therapy and eliminate ribavirin, use of a more potent third agent or a third agent with a different mechanism of action may be required.
- Subjects :
- Adult
Liver Cirrhosis
Male
0301 basic medicine
medicine.medical_specialty
Cirrhosis
Genotype
Sofosbuvir
Hepacivirus
Antiviral Agents
Gastroenterology
law.invention
03 medical and health sciences
chemistry.chemical_compound
Pharmacotherapy
Randomized controlled trial
law
Internal medicine
Humans
Medicine
Pharmacology (medical)
Aged
Pharmacology
Fluorenes
biology
business.industry
Ribavirin
Hepatitis C
Hepatitis C, Chronic
Middle Aged
medicine.disease
biology.organism_classification
030104 developmental biology
Infectious Diseases
chemistry
Benzimidazoles
Drug Therapy, Combination
Female
business
medicine.drug
Subjects
Details
- ISSN :
- 20402058 and 13596535
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Antiviral Therapy
- Accession number :
- edsair.doi.dedup.....4e7d5163e8f1ad250c7158594511e3e5