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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: LDV/SOF

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan
  • Chiayi City, Taiwan
  • Kaohsiung, Taiwan
  • Kaohsiung City, Taiwan
  • Keelung, Taiwan
  • Taichung, Taiwan
  • Tainan, Taiwan
  • Tainan City, Taiwan
  • Taipei, Taiwan
  • Taipei City, Taiwan
  • Taoyuan, Taiwan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF; LDV/SOF FDC for 12 weeks	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Patients With Chronic Hepatitis C and Hepatitis B Coinfection: a Phase 3 Study in Taiwan [Poster SAT-243]. EASL: The International Liver Congress; 2019 10-14 April; Vienna, Austria.
• Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Declines in HBsAg Levels Observed During Treatment With Ledispavir/Sofosbuvir in Patients With Chronic Hepatitis B Virus and Hepatitis C Virus Infection [Poster 1083]. The Liver Meeting® 2017 - The 68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October; Washington, D. C.
• Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, Chang TT, Massetto B, Yang JC, Yun C, Knox SJ, Osinusi A, Camus G, Jiang D, Brainard DM, McHutchison JG, Hu TH, Hsu YC, Lo GH, Chu CJ, Chen JJ, Peng CY, Chien RN, Chen PJ. Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV. Gastroenterology. 2018 Mar;154(4):989-997. doi: 10.1053/j.gastro.2017.11.011. Epub 2017 Nov 22.
• Liu CJ, Chuang WL, Sheen IS, Wang HY, Chen CY, Tseng KC, et al. Ledipasvir/Sofosbuvir for 12 Weeks Is Safe and Effective in Patients with Chronic Hepatitis C and Hepatitis B Coinfection: A Phase 3 Study in Taiwan [Presentation]. The International Liver Congress™ 2017: European Association for the Study of the Liver (EASL); 2017 19-23 April; Amsterdam, the Netherlands.
• Liu CJ, Sheen IS, Chen CY, Chuang WL, Wang HY, Tseng KC, Chang TT, Yang J, Massetto B, Suri V, Camus G, Jiang D, Zhang F, Gaggar A, Hu TH, Hsu YC, Lo GH, Chu CJ, Chen JJ, Peng CY, Chien RN, Chen PJ. Ledipasvir/Sofosbuvir for Patients Coinfected With Chronic Hepatitis C and Hepatitis B in Taiwan: Follow-up at 108 Weeks Posttreatment. Clin Infect Dis. 2022 Aug 31;75(3):453-459. doi: 10.1093/cid/ciab971.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): January 4, 2017
• Study Completion (Actual): November 7, 2018

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Coinfection; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: GS-US-337-1655

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes