Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the antiviral efficacy of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) therapy at the time of liver transplantation and through 4 weeks posttransplant in adults with genotype 1 or 4 hepatitis C virus (HCV) infection who are undergoing primary liver transplantation.

Official Title
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A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic HCV for Use in the Peri-Operative Liver Transplantation Setting

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: LDV/SOF


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide written informed consent or for those individuals where hepatic encephalopathy affects their ability to provide initial or ongoing consent, has an appropriate and legally-authorized representative (LAR) willing and able to provide consent on behalf of the individual. HCV RNA infection with quantifiable virus at screening Must have chronic genotype 1 or 4 HCV infection for ≥ 6 months by medical history or liver biopsy Currently on the liver transplantation wait list Screening electrocardiogram (ECG) without clinically significant abnormalities. A negative serum pregnancy test result is required for females Key Exclusion Criteria: Any previous solid organ transplant Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with participant's treatment, assessment, or compliance HIV infection or a positive hepatitis B virus surface antigen result History of malignancy (with exception of hepatocellular carcinoma within Milan criteria, certain resolved skin cancers or other early cancer for which surgical resection is considered to be completely curative) Treatment with any approved or experimental medication with known anti-HCV activity within 1 month prior to screening date Prior exposure to an HCV non-structural protein (NS)5A inhibitor Patients on hemodialysis prior to or at the time of transplantation will be excluded Creatinine clearance (CLcr) < 40 mL/min at screening or < 40 mL/min on day of transplant Participation in a clinical study with an investigational drug or biologic within 28 days prior to screening visit Receipt or planned receipt of an organ from an HCV positive donor Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDV/SOF<br>Participants with genotype 1 or 4 HCV who are undergoing liver transplant will receive one dose of LDV/SOF prior to the transplant and then will receive LDV/SOF once daily for 4 weeks following the transplant. | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally<br>* Other names: GS-5885/GS-7977;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event |  | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as: End of treatment virologic failure: Completed 28 days LDV/SOF treatment and had HCV RNA ≥ LLOQ at last measurement on treatment Virologic relapse: Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment HCV RNA measurement. | Up to Posttreatment Week 12 | 
| Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 |  | Days 1, 3, 5, 7, 14, 21, and 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver transplant, hepatitis C, Gilead, Communicable Diseases, Infection, Liver Diseases, RNA Virus Infections