Efficacy and Safety of Sofosbuvir/Ledipasvir ± Ribavirin in Japanese Participants With Chronic Genotype 1 HCV Infection

A Phase 3b, Randomized, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Treatment-Naïve and Treatment-Experienced Japanese Subjects With Chronic Genotype 1 HCV Infection

This study will evaluate the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV) fixed-dose combination (FDC) tablet with or without ribavirin (RBV) in treatment-naive or treatment-experienced Japanese participants with chronic genotype 1 HCV infection. Participants receive 12 weeks of treatment and continue assessments during a 24-week posttreatment follow-up period.

Study Overview

• Status: Completed
• Conditions: Chronic HCV Infection
• Intervention / Treatment: Drug: LDV/SOF; Drug: RBV

• Study Type: Interventional
• Enrollment (Actual): 341
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan, 010-0933
  • Chiba, Japan, 260-0856
  • Gifu, Japan, 500-8513
  • Okayama, Japan, 700-8558
  • Yamagata, Japan, 990-9585
  • Chiba
    • Ichikawa, Chiba, Japan, 272-8516
  • Fukuoka
    • Kurume, Fukuoka, Japan, 830-0011
  • Gifu
    • Ogaki, Gifu, Japan, 503-0864
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8621
  • Nagasaki
    • Omura, Nagasaki, Japan, 856-8562
  • Osaka
    • Suita, Osaka, Japan, 565-0871
  • Shizuoka
    • Izunokuni, Shizuoka, Japan, 410-2295
  • Tokyo
    • Chiyoda-ku, Tokyo, Japan, 101-8643
    • Itabashi-ku, Tokyo, Japan, 173-8610
    • Musashino, Tokyo, Japan, 180-8610
    • Shinjuku, Tokyo, Japan, 162-8566
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-0027

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

Inclusion Criteria:

• Body weight ≥ 40 kg
• HCV RNA ≥ 10^5 IU/mL at screening

Exclusion Criteria:

• Current or prior history of any clinically-significant illness (other than HCV)
• Pregnant or nursing female or male with pregnant female partner
• Chronic liver disease of a non-HCV etiology
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF (treatment naive); Treatment-naive participants will receive LDV/SOF for 12 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: GS-7977; PSI-7977; GS-5885
Experimental: LDV/SOF+RBV (treatment naive); Treatment-naive participants will receive LDV/SOF plus RBV for 12 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: GS-7977; PSI-7977; GS-5885; Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg); Other Names: Copegus®
Experimental: LDV/SOF (treatment experienced); Treatment-experienced participants will receive LDV/SOF for 12 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: GS-7977; PSI-7977; GS-5885
Experimental: LDV/SOF+RBV (treatment experienced); Treatment-experienced participants will receive LDV/SOF plus RBV for 12 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: GS-7977; PSI-7977; GS-5885; Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg); Other Names: Copegus®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 12 weeks
Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12), Treatment-naive, Noncirrhotic Participants	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants With Sustained Virologic Response at 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.	Posttreatment Weeks 4 and 24
Percentage of Participants Experiencing Virologic Failure	Virologic failure was defined as On-treatment virologic failure: Breakthrough (confirmed HCV RNA ≥ LLOQ 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) Virologic relapse: - Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.	Up to Posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Steven Knox, Gilead Sciences

Publications and helpful links

General Publications

• Mizokami M, Yokosuka O, Takehara T, Sakamoto N, Korenaga M, Mochizuki H, Nakane K, Enomoto H, Ikeda F, Yanase M, Toyoda H, Genda T, Umemura T, Yatsuhashi H, Ide T, Toda N, Nirei K, Ueno Y, Nishigaki Y, Betular J, Gao B, Ishizaki A, Omote M, Mo H, Garrison K, Pang PS, Knox SJ, Symonds WT, McHutchison JG, Izumi N, Omata M. Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial. Lancet Infect Dis. 2015 Jun;15(6):645-53. doi: 10.1016/S1473-3099(15)70099-X. Epub 2015 Apr 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: October 29, 2013
• First Submitted That Met QC Criteria: October 29, 2013
• First Posted (Estimate): November 5, 2013

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Communicable Diseases; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: GS-US-337-0113

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 http://www.gilead.com/research/disclosure-and-transparency.
• 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; SAP