Clinical trial NCT02613871: Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Adults With Chronic HCV and HBV Coinfection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 111
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants With Any Adverse Event Leading to Permanent Discontinuation of Study Drug
timeFrame: First dose date up to 12 weeks
Secondary outcomes:
measure: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With HCV RNA < LLOQ While on Treatment
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: Percentage of Participants With HCV RNA < LLOQ at Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108
timeFrame: Posttreatment Weeks 24, 36, 48, 60, 72, 84, 96, and 108
measure: HCV RNA Change From Baseline While on Treatment
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: Percentage of Participants With Virologic Failure
timeFrame: First dose date up to Posttreatment Week 12
measure: Plasma HBV DNA Change From Baseline While on Treatment
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: Plasma HBV DNA Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
timeFrame: Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
measure: HBsAg Level Change From Baseline While on Treatment
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: HBsAg Level Change From Baseline at Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
timeFrame: Posttreatment Weeks 4, 12, 24, 36, 48, 60, 72, 84, 96, and 108
measure: Serum LOXL-2 Level Change From Baseline While on Treatment
timeFrame: Weeks 1, 2, 4, 8, and 12
measure: Serum LOXL-2 Level Change From Baseline at Posttreatment Weeks 4, 12, and 36
timeFrame: Posttreatment Weeks 4, 12, and 36
measure: Percentage of Participants That Required HBV Therapy During the Study
timeFrame: First dose date up to Posttreatment Week 108
measure: Fibrosis Status as Assessed by Fibroscan Score at Posttreatment Weeks 12, 60, and 108
timeFrame: Posttreatment Weeks 12, 60, and 108
measure: Percentage of Participants That Develop Hepatocellular Carcinoma (HCC) During the Study
timeFrame: First dose date up to Posttreatment Week 108
Other outcomes:
Locations:
city: Changhua
country: Taiwan
city: Chiayi City
country: Taiwan
city: Kaohsiung City
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Keelung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan City
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei City
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
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 - The 68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October; Washington, D. C.
citation: 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.
citation: 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.
citation: 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.