Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Participants With Chronic Genotype 2 HCV Infection

A Phase 3b, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 2 HCV Infection

The primary objectives of this study are to evaluate the antiviral efficacy of therapy with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) and to evaluate the safety and tolerability of LDV/SOF FDC and sofosbuvir (SOF) + ribavirin (RBV) in participants with chronic genotype 2 hepatitis C virus (HCV) infection.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Bunkyo, Japan
  • Chiba, Japan
  • Chuo City, Japan
  • Ehime, Japan
  • Fukuoka, Japan
  • Fukuyama, Japan
  • Gifu, Japan
  • Ibaragi, Japan
  • Ikeda, Japan
  • Iruma-gun, Japan
  • Itabashi, Japan
  • Izunokuni, Japan
  • Kagoshima, Japan
  • Kashihara, Japan
  • Kitakyushu, Japan
  • Kumamoto, Japan
  • Kyoto, Japan
  • Maebashi, Japan
  • Matsumoto, Japan
  • Morioka, Japan
  • Musashino, Japan
  • Nagasaki, Japan
  • Nagoya, Japan
  • Nishinomiya, Japan
  • Ogaki City, Japan
  • Okayama, Japan
  • Omura, Japan
  • Osaka, Japan
  • Saga, Japan
  • Sagamihara, Japan
  • Sapporo, Japan
  • Sendai, Japan
  • Suita, Japan
  • Takamatsu, Japan
  • Ube, Japan
  • Yamagata, Japan
  • Yufu, Japan

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:

• Chronic genotype 2 HCV-infected males and non-pregnant/non-lactating females
• Aged 20 years or older
• Treatment naive or treatment experienced
• At least 20 subjects will have Child-Pugh-A compensated cirrhosis. In Cohort 2, participants must be ineligible or intolerant of RBV.

Key Exclusion Criteria:

• Previous exposure to an NS5A or NS5B inhibitor
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• Pregnant or nursing female or male with pregnant female partner

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF (Cohort 1); 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
Experimental: SOF+RBV (Cohort 1); SOF+RBV for 12 weeks	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Capsules 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: REBETOL®
Experimental: LDV/SOF (Cohort 2); Participants who are ineligible for or intolerant to RBV therapy will receive 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 quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event		Up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HCV RNA < LLOQ at Week 2		Week 2
Percentage of Participants With HCV RNA < LLOQ at Week 4		Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 8		Week 8
Percentage of Participants With HCV RNA < LLOQ at Week 12		Week 12
Change From Baseline in HCV RNA at Week 2		Baseline; Week 2
Change From Baseline in HCV RNA at Week 4		Baseline; Week 4
Change From Baseline in HCV RNA at Week 8		Baseline; Week 8
Change From Baseline in HCV RNA at Week 12		Baseline; Week 12
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.	Posttreatment Week 4
Percentage of Participants With HCV RNA < LLOQ at Week 1		Week 1
Percentage of Participants With HCV RNA < LLOQ at Week 6		Week 6
Percentage of Participants With Overall 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), orRebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), orNon-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
Change From Baseline in HCV RNA at Week 1		Baseline; Week 1
Change From Baseline in HCV RNA at Week 6		Baseline; Week 6
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	SVR 24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.	Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ at Week 3		Week 3
Percentage of Participants With HCV RNA < LLOQ at Week 5		Week 5
Percentage of Participants With HCV RNA < LLOQ at Week 10		Week 10
Change From Baseline in HCV RNA at Week 3		Baseline; Week 3
Change From Baseline in HCV RNA at Week 5		Baseline; Week 5
Change From Baseline in HCV RNA at Week 10		Baseline; Week 10

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2016
• Primary Completion (Actual): February 14, 2017
• Study Completion (Actual): May 11, 2017

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimate): April 14, 2016

Study Record Updates

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

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-337-1903

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

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