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

Phase 3

Completed

• Conditions: Hepatitis C Virus Infection
• Interventions: Drug: LDV/SOF

• Registration Number: NCT02613871
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-23
• Study First Submitted QC: 2015-11-23
• Study First Posted: 2015-11-25
• Study Start: 2015-12-22
• Primary Completion: 2017-01-04
• Results First Submitted: 2018-01-03
• Results First Submitted QC: 2018-02-12
• Results First Posted: 2018-02-13
• Study Completion: 2018-11-07
• Status Verified: 2019-11
• Last Update Submitted: 2020-02-18
• Last Update Posted: 2020-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LDV/SOF	LDV/SOF	LDV/SOF FDC for 12 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantification (LLOQ; 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug	First dose date up to 12 weeks

Secondary Outcome Measures

Name	Time	Method
Plasma HBV DNA 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
HCV RNA Change From Baseline While on Treatment	Weeks 1, 2, 4, 8, and 12
Percentage of Participants With HCV RNA < LLOQ While on Treatment	Weeks 1, 2, 4, 8, and 12	LLOQ = 15 IU/mL
Percentage of Participants With Virologic Failure	First dose date up to Posttreatment Week 12	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)
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
Serum LOXL-2 Level Change From Baseline While on Treatment	Weeks 1, 2, 4, 8, and 12
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	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
Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study	First dose date up to Posttreatment Week 108
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	Posttreatment Week 4	SVR4 was defined as HCV RNA \< LLOQ (15 IU/mL) at 4 weeks after stopping study treatment.
Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108	Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108	LLOQ = 15 IU/mL
Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36	Posttreatment Weeks 4, 12, and 36