All Clinical Trials
Filter by Category
- All Clinical Trials
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Resistance/Virological Failure
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
- Pharmacology
Official Title Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt.
Purpose / DescriptionThis open-label multicenter study evaluated the efficacy of ledipasvir-sofosbuvir, with or without ribavirin, for 8 or 12 weeks in 256 Egyptian adults with HCV genotype 4 infection; 170 were treatment naïve and 85 were treatment experienced. For the treatment-naïve participants without cirrhosis who received 8 weeks of therapy, 97% (35 of 36) of those receiving ledipasvir-sofosbuvir achieved an SVR12, compared with 91% (32 of 35) who received ledipasvir-sofosbuvir plus ribavirin. Using 12 weeks of therapy in treatment-naïve patients without cirrhosis, the SVR12 rates were 100% (34 of 34) in the ledipasvir-sofosbuvir arm and 97% (33 of 34) with ledipasvir-sofosbuvir plus ribavirin. For treatment-naïve individuals with compensated cirrhosis, the SVR12 rates were 100% (8 of 8) with 12 weeks of ledipasvir-sofosbuvir plus ribavirin; all other regimens had SVR12 rates less than 90%, but the number of persons with cirrhosis in the treatment-naïve group was small.
Phase Phase III
ClinicalTrials.gov NCT02487030
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Shiha G, Esmat G, Hassany M, et al. Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt. Gut. 2019;68:721-8.
Official Title Efficacy of Nucleotide Polymerase Inhibitor Sofosbuvir plus the NS5A Inhibitor Ledipasvir or the NS5B Non-Nucleoside inhibitor GS-9669 Against HCV Genotype 1 Infection.
Purpose / DescriptionIn this phase 2, open-label study, which involved seven arms (12-17, and 22) of the parent ELECTRON study, investigators compared an array of all-oral regimens, most of which included ledipasvir and sofosbuvir; six of the seven regimens included ribavirin and two included GS-9669. A total of 113 patients were enrolled in the seven arms of this study and the groups included treatment-naive noncirrhotics, treatment-experienced (with prior null response) noncirrhotics, and treatment experienced (with prior null response) cirrhotics. All of the regimens were taken for a duration of 12 weeks, except for the 6-week regimen of ledipasvir-sofosbuvir plus ribavirin, which was used in noncirrhotic treatment-naive patients. All of the groups that received ledipasvir plus sofosbuvir plus ribavirin had very high SVR rates, except for the group that received only 6 weeks of therapy. The ledipasvir plus GS-9669 plus ribavirin regimen also performed very well.
Phase Phase II
ClinicalTrials.gov NCT01260350
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Gane EJ, Stedman CA, Hyland RH, et al. Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection. Gastroenterology. 2014;146:736-43.
Official Title Effectiveness, Treatment Completion and Safety of Sofosbuvir-Ledipasvir and Paritaprevir-Ritonavir-Ombitasvir plus Dasabuvir in Patients with Chronic Kidney Disease: an ERCHIVES Study.
Purpose / DescriptionIn an observational cohort study conducted in the Veterans Administration system, investigators used the Electronically Retrieved Cohort of HCV-Infected Persons (ERCHIVES) to analyze HCV treatment responses for 13,663 persons who received ledipasvir-sofosbuvir, with or without ribavirin. This cohort included a total of 1,607 with CKD stage 3, 4, or 5 who completed HCV treatment.[25] The SVR12 rates for individuals with stage 3 CDK who completed treatment was 97.0% (1080 of 1113) in those who received ledipasvir-sofosbuvir and 97.1% (375 of 386) with ledipasvir-sofosbuvir plus ribavirin. For those with stage 4 or 5 CKD, the SVR12 rates were 94.0% (78 of 83) with ledipasvir-sofosbuvir and 100% (25 of 25) with ledipasvir-sofosbuvir plus ribavirin. The ERCHIVES-Renal also included analysis of persons with CKD and HCV treatment responses to ombitasvir-paritaprevir-ribavirin and dasabuvir, with or without ribavirin.
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryMerck Sharp & Dohme Corp.
Non-IndustryVA Pittsburgh Healthcare System.
References
- Butt AA, Ren Y, Puenpatom A, Arduino JM, Kumar R, Abou-Samra AB. Effectiveness, treatment completion and safety of sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir + dasabuvir in patients with chronic kidney disease: an ERCHIVES study. Aliment Pharmacol Ther. 2018;48:35-43.
Official Title Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Purpose / DescriptionIn this open-label phase 3 trial, investigators enrolled 865 treatment-naive patients with genotype 1 chronic hepatitis C and compared a 12- and 24-week treatment course of the fixed-dose combination of ledipasvir-sofosbuvir, given with our without ribavirin. In this study, patients with compensated cirrhosis were eligible to enroll (up to 20% of the total study participants could have cirrhosis). All treatment arms had SVR12 rates greater than 95% and no differences were observed in the 12-week versus the 24-week treatment course. In addition, use of ribavirin did not improve SVR rates. Further, patients with cirrhosis had similar SVR rates as those without cirrhosis. This study clearly established that a 12-week course of the fixed-dose combination ledipasvir-sofosbuvir, without ribavirin, is highly effective in treatment-naive patients with chronic HCV genotype 1 infection, including those with cirrhosis.
Phase Phase III
ClinicalTrials.gov NCT01701401
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Afdhal N, Zeuzem S, Kwo P, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889-98.
Official Title Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection.
Purpose / DescriptionIn the ION-2 trial, investigators randomized 440 treatment-experienced patients with genotype 1 chronic hepatitis C infection to receive a 12- or 24-week treatment with fixed-dose combination ledipasvir-sofosbuvir, with or without ribavirin. Patients were considered treatment-experienced if they had not achieved an SVR with a previous regimen of peginterferon plus ribavirin, with or without an NS3/4A protease inhibitor. For the treatment experienced patients, 41 to 46% had a prior nonresponse (null responder). Patients were allowed to enroll if they had cirrhosis, but the number of patients with cirrhosis enrolled could not exceed 20% of the total enrolled. The SVR12 rate with 12 weeks of ledipasvir-sofosbuvir was 94% without ribavirin and 96% with ribavirin. Both groups of patients who received 24 weeks of therapy had an SVR12 rate of 99%. For patients with cirrhosis, the SVR rates were lower with 12 weeks of therapy (86% with ledipasvir-sofosbuvir and 82% with ledipasvir-sofosbuvir with ribavirin) compared with the respective 95% and 100% SVR rates with 12 weeks in patients who did not have cirrhosis. The SVR rates were 99 to 100% in both treatment groups receiving 24 weeks of therapy, including those with cirrhosis. The investigators clearly established that ledipasvir-sofosbuvir is highly effective in treatment-experienced patients, even those who previously received an NS34A protease inhibitor. Treatment-experienced patients with cirrhosis may benefit by extending treatment duration from 12 to 24 weeks.
Phase Phase III
ClinicalTrials.gov NCT01768286
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014;370:1483-93.
Official Title Ledipasvir and Sofosbuvir for 8 or 12 Weeks for Chronic HCV without Cirrhosis
Purpose / DescriptionIn this open-label phase 3 trial, investigators randomized 647 treatment-naive patients with genotype 1 chronic hepatitis C to one of three regimens that included the fixed-dose combination of ledipasvir-sofosbuvir: 8 weeks of ledipasvir-sofosbuvir, 8 weeks of ledipasvir-sofosbuvir plus ribavirin, or 12 weeks of ledipasvir-sofosbuvir. Patients with cirrhosis were not eligible to enroll. Similar SVR12 rates were observed in the three treatment arms: 94% with 8 weeks of ledipasvir-sofosbuvir, 93% with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% with 12 weeks of ledipasvir-sofosbuvir. A subanalysis showed that a pre-treatment HCV RNA level less than 6 million IU/mL correlated with higher SVR12 rates in the group that received 8 weeks of ledipasvir-sofosbuvir. This study has shown that (1) ledipasvir-sofosbuvir is highly effective in treatment-naive genotype 1 patients without cirrhosis and (2) an 8-week treatment course is a reasonable and more cost-effective option for treatment-naive patients without cirrhosis if they have a baseline HCV RNA less than 6 million IU/mL.
Phase Phase III
ClinicalTrials.gov NCT01851330
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014;370:1879-88.
Official Title Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1
Purpose / DescriptionIn this phase 3, open-label, multicenter study in the United States, Canada, and New Zealand, investigators enrolled 335 patients with hepatitis C and HIV coinfection to receive a 12-week course of ledipasvir-sofosbuvir. Enrollment included genotype 1 or 4 HCV treatment-naive and experienced patients without cirrhosis and those with compensated cirrhosis. The HIV enrollment criteria consisted of HIV RNA less than 50 copies/ml and CD4 count greater than 100 cells/mm3. The antiretroviral regimens that were allowed consisted of tenofovir-emtricitabine plus either efavirenz, rilpivirine, or raltegravir. Most (98%) of the patients enrolled had genotype 1 HCV infection and 55% were treatment experienced. Overall, 321 (96%) of 335 treated patients achieved an SVR12. The results were similar regardless of prior treatment status or presence of cirrhosis.
Phase Phase III
ClinicalTrials.gov NCT02073656
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373:705-13.
Official Title Sofosbuvir and Ledipasvir Fixed-Dose Combination with and without Ribavirin in Treatment-Naive and Previously Treated Patients with Genotype 1 Hepatitis C Virus Infection (LONESTAR): an Open-Label, Randomised, Phase 2 Trial
Purpose / DescriptionThis phase 2 trial evaluated 8- and 12-week courses of the fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg), with or without ribavirin (weight based dose of 1000 to 1200 mg/day divided BID) in treatment-naive and treatment experienced patients wtih chronic HCV genotype 1 infection. The study enrolled a total of 100 patients, 60 who were treatment naïve (Cohort A) and 40 who had previously failed prior therapy with an HCV protease inhibitor-based regimen (Cohort B). Among the treatment-experienced patients, 55% had documented, compensated cirrhosis. The study included 5 treatment arms and a total of 100 patients. In all of the five study arms, SVR12 was achieved in 95 to 100% of patients. The regimen of ledipasvir-sofosbuvir was well tolerated; only one patient had a serious adverse event of anemia, thought to be related to ribavirin. This study clearly showed that the fixed-dose combination of ledipasvir-sofosbuvir with or without ribavirin is highly effective in treatment-naive and treatment-experienced patients.
Phase Phase II
ClinicalTrials.gov NCT01329978
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383:515-23.
Official Title Efficacy of Ledipasvir and Sofosbuvir, with or without Ribavirin, for 12 Weeks inPatients with HCV Genotype 3 or 6 Infection
Purpose / DescriptionIn the open-label, phase 2 New Zealand Genotype 3 and 6 trial, investigators enrolled 126 patients with chronic hepatitis C infection to receive a 12 weeks of treatment with fixed-dose combination ledipasvir-sofosbuvir, with or without ribavirin. Four groups were enrolled: (a) treatment-naive patients with genotype 3 infection who received ledipasvir-sofosbuvir, (b) (a) treatment-naive patients with genotype 3 infection who received ledipasvir-sofosbuvir plus ribavirin, (c) treatment-experienced patients with genotype 3 infection who received ledipasvir-sofosbuvir plus ribavirin, and (d) treatment-naive and -experienced patients with genotype 6 infection who received ledipasvir-sofosbuvir. The SVR 12 responses in treatment-naive patients with genotype 3 were superior in the regimen with ribavirin (100%) than without ribavirin (64%). Among the treatment-experienced patients, 41 (82%) of 50 achieved an SVR 12 with a regimen of ledipasvir-sofosbuvir plus ribavirin. The SVR 12 rate was 96% in the patients with genotype 6. In this trial, the investigators showed that patients with genotype 3 had very good SVR 12 rates with ledipasvir-sofosbuvir plus ribavirin and those with genotype 6 responded well to ledipasvir-sofosbuvir plus ribavirin without ribavirin.
Phase Phase II
ClinicalTrials.gov NCT01826981
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Gane EJ, Hyland RH, An D, et al. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology. 2015;149:1454-1461.e1.
Official Title Virologic Response following Combined Ledipasvir and Sofosbuvir Administration in Patients with HCV Genotype 1 and HIV Co-Infection
Purpose / DescriptionERADICATE is an open-label, nonrandomized, phase 2 trial investigating the safety and efficacy of a 12-week regimen of ledipasvir-sofosbuvir in HCV treatment-naive patients with genotype 1 chronic hepatitis C who are coinfected with HIV. The study enrolled 50 patients and divided them into two cohorts: (a) those not receiving antiretroviral therapy (n=13), and (b) those receiving antiretroviral therapy (n=37). The patients on antiretroviral therapy were allowed to receive tenofovir-emtricitabine plus either efavirenz, raltegravir, rilpivirine, rilpivirine plus raltegravir, or efavirenz plus raltegravir. Data for patients not taking antiretroviral therapy showed 13 (100%) of 13 achieved an SVR12. For patients taking antiretroviral therapy, 36 (97%) of 37 achieved an SVR12. These findings suggest that ledipasvir-sofosbuvir is very effective in patients with genotype 1 HCV and HIV coinfection. The hepatitis C regimen was well tolerated and no patient discontinued hepatitis C therapy.
Phase Phase II
ClinicalTrials.gov NCT01878799
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
Non-IndustryNational Institute of Allergy and Infectious Diseases (NIAID)
References
- Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313:1232-9.
Official Title Re-Treatment of Chronic Hepatitis C Virus Genotype 1 Infection after Relapse: an Open-Label Pilot Study.
Purpose / Description
This open-label, phase 2a trial enrolled patients with genotype 1 HCV who previously had failed a 24-week course of sofosbuvir plus ribavirin and retreated them using fixed-dose combination of ledipasvir-sofosbuvir for 12 weeks. A total of 14 patients enrolled and all had prior relapse as the cause of treatment failure. Among the 14 patients, 13 were male and 13 were black. One half of those enrolled had advanced fibrosis (Knodell Histology Activity Index score of 3 or 4). The virologic response rates were excellent, with 14 (100%) of 14 patients achieving an SVR12. This small study is very promising but should be confirmed by larger future studies, which could include prior nonresponders.
Phase Phase II
ClinicalTrials.gov NCT01805882
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
Non-IndustryNational Institute of Allergy and Infectious Diseases (NIAID)
References
- Osinusi A, Kohli A, Marti MM, et al. Re-treatment of chronic hepatitis C virus genotype 1 infection after relapse: an open-label pilot study. Ann Intern Med. 2014;161:634-8.
Official Title Virological Response after 6 Week Triple-Drug Regimens for Hepatitis C: a Proof-of-Concept Phase 2A Cohort Study
Purpose / DescriptionThe NIAID SYNERGY (Genotype 1) trial was an open-label, phase 2a trial that enrolled 60 treatment-naive patients with genotype 1 chronic HCV to receive one of three treatment groups: (a) ledipasvir-sofosbuvir for 12 weeks; (b) ledipasvir-sofosbuvir (90-400 mg) plus the non-nucleoside NS5B inhibitor GS-9669 (500 mg once daily) for 6 weeks, or (c) ledipasvir-sofosbuvir (90-400 mg) plus the NS3/4A protease inhibitor GS-9451 (80 mg once daily) for 6 weeks. Patients in the 12-week ledipasvir-sofosbuvir arm with any stage of fibrosis could be enrolled in the study. For the other two treatment arms, patients were excluded if they had cirrhosis. Overall, patients in all three arms of the study had excellent SVR12 rates: 20 (100%) of 20 patients in the ledipasvir-sofosbuvir arm, 19 (95%) of 20 in the ledipasvir-sofosbuvir plus GS-9669 group, and 19 (95%) of 20 in the ledipasvir-sofosbuvir plus GS-9451 group. This study demonstrates that (1) patients with genotype 1 chronic HCV achieve very high SVR rates with a 12-week course of ledipasvir-sofosbuvir and (2) ledipasvir-sofosbuvir, when combined with a third direct-acting antiviral agent, is highly effective as a short-course 6 week regimen in treatment-naive patients without cirrhosis.
Phase Phase II
ClinicalTrials.gov NCT01805882
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
Non-IndustryNational Institute of Allergy and Infectious Diseases (NIAID)
References
- Kohli A, Osinusi A, Sims Z, et al. Virological response after 6 week triple-drug regimens for hepatitis C: a proof-of-concept phase 2A cohort study. Lancet. 2015;385:1107-13.
Official Title Ledipasvir and Sofosbuvir for Hepatitis C Genotype 4: a Proof-of-Concept, Single-Centre, Open-Label Phase 2a Cohort Study
Purpose / DescriptionThe NIAID SYNERGY (Genotype 4) trial was an open-label, phase 2a trial that enrolled 21 patients with genotype 4 chronic HCV to receive ledipasvir-sofosbuvir for 12 weeks. Among those enrolled, 13 (68%) were treatment-naive and 8 (32%) were treatment-experienced. The treatment-experienced patients previously had received an interferon- or peginterferon-based regimen. Patients with compensated cirrhosis were allowed to enroll in the study and 7 (33%) of 21 had cirrhosis. Overall, in the intent-to-treat analysis 20 (95%) of 21 patients achieved an SVR12. One patient, a treatment-naive patient, was considered a treatment failure and withdrew from the study at week 7 due to non-adherence with therapy.
Phase Phase II
ClinicalTrials.gov NCT01805882
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
Non-IndustryNational Institute of Allergy and Infectious Diseases (NIAID)
References
- Kohli A, Kapoor R, Sims Z, et al. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infect Dis. 2015;15:1049-54.
Official Title Ledipasvir-Sofosbuvir plus Ribavirin for Patients with Genotype 1 Hepatitis C Virus Previously Treated in Clinical Trials of Sofosbuvir Regimens
Purpose / DescriptionIn this open-label, phase 2 trial, patients with genotype 1 chronic HCV who failed a sofosbuvir-containing regimen in a phase 2 or 3 Gilead-sponsored clinical trial were eligible to receive retreatment with a 12-week course of ledipasvir-sofosbuvir plus ribavirin. Patients with compensated cirrhosis were allowed to enroll in the study (27% of patients enrolled had cirrhosis). Among the patients treated with ledipasvir-sofosbuvir plus ribavirin, 50 (98%) of 51 achieved an SVR12; the one patient who failed had genotype 3 HCV and was erroneously enrolled in the trial. Overall, the 12-week regimen of ledipasvir-sofosbuvir plus ribavirin was well tolerated and it shows promise as a treatment option for patients with prior sofosbuvir failure.
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Wyles D, Pockros P, Morelli G, et al. Ledipasvir-sofosbuvir plus ribavirin for patients with genotype 1 hepatitis C virus previously treated in clinical trials of sofosbuvir regimens. Hepatology. 2015;61:1793-7.
Official Title Ledipasvir-sofosbuvir with or without Ribavirin to Treat Patients with HCV Genotype 1 Infection and Crrhosis Non-Responsive to Previous Protease-Inhibitor Therapy: a Randomised, Double-Blind, Phase 2 Trial (SIRIUS)
Purpose / DescriptionThis phase 2, double-blind trial compared the efficacy of a 12-week course of ledipasvir-sofosbuvir plus ribavirin versus a 24-week course of ledipasvir-sofosbuvir in treatment-experienced patients with genotype 1 HCV and compensated cirrhosis. Investigators enrolled 155 patients in the trial and all had previously sequentially failed dual therapy with peginterferon and ribavirin and triple therapy with peginterferon and ribavirin and an NS3/4A protease inhibitor. One patient dropped out of the study due to an adverse event that occurred while receiving placebo. Among patients who received a 12-week course of ledipasvir-sofosbuvir plus ribavirin, 96% achieved and SVR12 compared with 97% in the group that received a 24-week course of ledipasvir-sofosbuvir. Baseline NS5A resistant-associated variants did not significantly impact treatment response. This study suggests that in genotype 1 treatment-experienced patients with cirrhosis, a 12-week course of ledipasvir-sofosbuvir plus ribavirin provides similar SVR12 rates as a 24-week course of ledipasvir-sofosbuvir and this 12-week regimen provides a more cost-effective option.
Phase Phase II
ClinicalTrials.gov NCT01965535
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Bourlière M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis. 2015;15:397-404.
Official Title Ledipasvir and Sofosbuvir plus Ribavirin for Treatment of HCV Infection in Patients with Advanced Liver Disease.
Purpose / DescriptionIn this phase 2, open label trial, 337 patients with HCV genotype 1 or 4 and advanced liver disease were randomized to receive either a 12-week or 24-week course of ledipasvir-sofosbuvir plus ribavirin. The study included two cohorts: the cohort A (pretransplantation) arm of the study enrolled patients with cirrhosis and moderate to severe hepatic impairment; cohort B consisted of patients who were post liver transplantation. Patients were also stratified based on no cirrhosis, Child-Turcotte-Pugh (CTP) class A, B or Class C, and fibrosing cholestatic hepatitis. In the cohort A (pre-transplant) group, the SVR12 rate was 87% in the 12-week arm and 89% in the 24-week arm. In the cohort B (post-transplant) group, SVR12 results with combined 12 and 24 week data show clearly better in patients with less advanced liver disease: 96% in CTP A versus 87% in CTP B versus 67% in CTP C. The results were similar with either 12- or 24 weeks of treatment except for patients with CTP C: nine post-transplant patients with CTP C received therapy and SVR rates 60% with 12 weeks of therapy and 75% with 24 weeks. The treatment was well-tolerated and there were few treatment-related adverse events. The patients with virologic response had significant improvement in liver function, including improvements in bilirubin, albumin, Modified End Stage Liver Disease (MELD) scores, and Child-Turcotte-Pugh scores. These results are very promising for the treatment of patients with advanced liver disease, including post-transplantation patients, and it appears that a 12-week course is equivalent to the 24-week course, except perhaps with patients who have CTP C liver disease.
Phase Phase II
ClinicalTrials.gov NCT01938430
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Charlton M, Everson GT, Flamm SL, et al. Ledipasvir and sofosbuvir plus ribavirin for treatment of HCV infection in patients with advanced liver disease. Gastroenterology. 2015;149:649-59.
Official Title Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial
Phase Phase II
ClinicalTrials.gov NCT02010255
Treatments
Ledipasvir-Sofosbuvir

Ledipasvir-Sofosbuvir
Tradename:HarvoniOther Names:LDV-SOFClass:FDA-ApprovedFunding
IndustryGilead Sciences
References
- Manns M, Samuel D, Gane EJ, et al. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016;16:685-97.
Editor's Summary
A PDF version of this treatment drug's summary, including the clinical trial descriptions and references.
Ledipasvir-Sofosbuvir Slide Deck
December 4, 2020
Clinical Trial Image Decks
Egyptian GT4 Multicenter Study - October 6, 2020
ELECTRON (Arms 12-17 and 22) - July 29, 2020
ERCHIVES-Renal - July 29, 2020
ION-1 - July 29, 2020
ION-2 - July 29, 2020
ION-3 - July 29, 2020
ION-4 - July 29, 2020
LONESTAR - July 26, 2020
New Zealand Genotype 3 and 6 Trial - July 29, 2020
NIAID ERADICATE - July 29, 2020
NIAID Retreatment of Sofosbuvir Failures (Genotype 1) PDF NIAID Retreatment of Sofosbuvir Failures (Genotype 1) PPTX
NIAID Retreatment of Sofosbuvir Failures (Genotype 1) - July 29, 2020
NIAID SYNERGY (Genotype 1) - July 29, 2020
NIAID SYNERGY (Genotype 4) - July 29, 2020
Retreatment of Sofosbuvir Failures from prior Clinical Trials PDF Retreatment of Sofosbuvir Failures from prior Clinical Trials PPTX
Retreatment of Sofosbuvir Failures from prior Clinical Trials - July 29, 2020
SIRIUS - July 29, 2020
SOLAR-1: (Cohorts A and B) - July 29, 2020
SOLAR-2 - December 4, 2020