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

Hepatitis C Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02613871
• Other study ID #: GS-US-337-1655
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2015
• Est. completion date: November 7, 2018

Study information

• Verified date: November 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: November 7, 2018
• Est. primary completion date: January 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Coinfection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Virus Diseases

Intervention

Drug:
• LDV/SOF
90/400 mg FDC tablet administered orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

Taiwan, 

References & Publications (4)

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 — View Citation

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

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

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 Co

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug		First dose date up to 12 weeks
Secondary	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
Secondary	Percentage of Participants With HCV RNA < LLOQ While on Treatment	LLOQ = 15 IU/mL	Weeks 1, 2, 4, 8, and 12
Secondary	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
Secondary	HCV RNA Change From Baseline While on Treatment		Weeks 1, 2, 4, 8, and 12
Secondary	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
Secondary	Plasma HBV DNA Change From Baseline While on Treatment		Weeks 1, 2, 4, 8, and 12
Secondary	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
Secondary	HBsAg Level Change From Baseline While on Treatment		Weeks 1, 2, 4, 8, and 12
Secondary	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
Secondary	Serum LOXL-2 Level Change From Baseline While on Treatment		Weeks 1, 2, 4, 8, and 12
Secondary	Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36		Posttreatment Weeks 4, 12, and 36
Secondary	Percentage of Participants That Required HBV Therapy During the Study		First dose date up to Posttreatment Week 108
Secondary	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
Secondary	Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study		First dose date up to Posttreatment Week 108