Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Adults With Chronic HCV and HBV Coinfection

Study Overview
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Brief Summary
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The primary objectives of this study are to determine the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in adults with chronic genotype 1 or 2 HCV infection who are coinfected with HBV in Taiwan.

Official Title
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A Phase 3b Open-Label Study of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 2 Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) Coinfection

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: Individuals ≥ 40 kg in weight with chronic genotype 1 or 2 HCV and HBV coinfection Individuals must not be taking or requiring treatment with HBV antiviral therapy at screening. For participants that are HBV treatment experienced, the most recent treatment must have been completed at least 6 months prior to Day 1. Cirrhosis determination by Fibroscan Screening laboratory values within defined thresholds Use of two effective contraception methods if female or male is of childbearing potential Key Exclusion Criteria: Current or prior history of clinically-significant illness or any other major medical disorder that may interfere with individual's treatment, assessment or compliance with the protocol Pregnant or nursing female Infection with human immunodeficiency virus (HIV) or hepatitis delta virus (HDV) Hepatocellular carcinoma (HCC) or other malignancy Current or prior history of clinical hepatic decompensation Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 20 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>LDV/SOF FDC for 12 weeks | Drug: LDV/SOF<br>* 90/400 mg FDC tablet administered orally once daily<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 quantification (LLOQ; 15 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 | 
| Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug |  | First dose date up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ (15 IU/mL) at 4 weeks after stopping study treatment. | Posttreatment Week 4 | 
| Percentage of Participants With HCV RNA < LLOQ While on Treatment | LLOQ = 15 IU/mL | Weeks 1, 2, 4, 8, and 12 | 
| Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108 | LLOQ = 15 IU/mL | Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108 | 
| HCV RNA Change From Baseline While on Treatment |  | Weeks 1, 2, 4, 8, and 12 | 
| Percentage of Participants With Virologic Failure | Virologic failure was defined as : Breakthrough (confirmed HCV RNA ≥ LLOQ [15 IU/mL] after having previously had HCV RNA < LLOQ while on treatment), or Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment), or Relapse (HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement) | First dose date up to Posttreatment Week 12 | 
| Plasma HBV DNA Change From Baseline While on Treatment |  | Weeks 1, 2, 4, 8, and 12 | 
| Plasma HBV DNA Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |  | Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 | 
| HBsAg Level Change From Baseline While on Treatment |  | Weeks 1, 2, 4, 8, and 12 | 
| HBsAg Level Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 |  | Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108 | 
| Serum LOXL-2 Level Change From Baseline While on Treatment |  | Weeks 1, 2, 4, 8, and 12 | 
| Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36 |  | Posttreatment Weeks 4, 12, and 36 | 
| Percentage of Participants That Required HBV Therapy During the Study |  | First dose date up to Posttreatment Week 108 | 
| Fibrosis Status as Assessed by Fibroscan Score at Posttreatment Weeks 12, 60, and 108 | FibroScan is a non-invasive device that assesses the hardness (or stiffness) of the liver using the technique of transient elastography. FibroScan results range from 2.5 kPa to 75 kPa with higher scores indicating greater liver stiffness. Per protocol, cirrhosis status was determined as follows: Presence of cirrhosis = FibroScan result of > 12.5 kPa Absence of cirrhosis = FibroScan result of ≤ 12.5 kPa | Posttreatment Weeks 12, 60, and 108 | 
| Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study |  | First dose date up to Posttreatment Week 108 |