Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection in Participants With Chronic Genotype 1, 2, 3, or 6 HCV Infection

A Phase 2, Multicenter, Open-Label Study to Assess the Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection

The purpose of this study is to evaluate the antiviral efficacy, safety, tolerability of combination therapy with sofosbuvir (SOF) containing regimens for the treatment of chronic hepatitis C virus (HCV) infection.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: RBV; Drug: LDV/SOF; Drug: SOF; Drug: Peg-IFN; Drug: GS-9669; Drug: VEL

• Study Type: Interventional
• Enrollment (Actual): 359
• Phase: Phase 2

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies Ltd.
  • Christchurch, New Zealand
    • Christchurch Clinical Studies Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic genotype 1, 2, 3, or 6 HCV infection
• Cirrhosis determination; a liver biopsy may be required
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Pregnant or nursing female or male with pregnant female partner
• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
• Chronic use of systemic immunosuppressive agents
• History of clinically significant illness or any other medical disorder that may interfere with the individual's treatment, assessment or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1,Group 1: LDV/SOF + RBV 12 wk (GT1 SOF retreatment); LDV/SOF + RBV for 12 weeks in participants with genotype 1 HCV infection and who failed to achieve sustained virologic response (SVR) in a previous Gilead sofosbuvir study	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 1,Group 2:SOF+Peg-IFN+RBV 12 wk (GT2,3 SOF retreatment); SOF + PEG + RBV for 12 weeks in participants with genotype 2 or 3 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: SOF; SOF 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; Drug: Peg-IFN; pegylated interferon (Peg-IFN) 180 µg administered subcutaneously once weekly; Other Names: Pegasys®
EXPERIMENTAL: Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, liver disease); LDV/SOF+RBV for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 2,Group 2: LDV/SOF+GS-9669 12wk (GT1 TE, liver disease); LDV/SOF + GS-9669 for 12 weeks in treatment-experienced participants with genotype 1 HCV infection and advanced liver fibrosis or compensated liver fibrosis	Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977; Drug: GS-9669; GS-9669 500 mg (2 × 250 mg tablet) administered orally once daily
EXPERIMENTAL: Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN); LDV/SOF for 12 weeks in treatment-naive participants with genotype 3 HCV infection	Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 2,Group 4: LDV/SOF+RBV 12 wk (GT3 TN); LDV/SOF + RBV for 12 weeks in treatment-naive participants with genotype 3 HCV infection	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 2,Group 5: LDV/SOF 12 wk (GT6 TE/TN); LDV/SOF for 12 weeks in treatment-naive or treatment-experienced participants with genotype 6 HCV infection	Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 2,Group 6: LDV/SOF+RBV 12 wk (GT3 TE); LDV/SOF + RBV for 12 weeks in treatment-experienced participants with genotype 3 HCV infection	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 3,Group 1: LDV/SOF 12 wk (GT1 cirrhotic CPT B); LDV/SOF for 12 weeks in participants with genotype 1 HCV infection and Child-Pugh Turcotte (CPT) B cirrhosis	Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 4,Group 1: SOF+VEL 25mg 8 wk (GT3 TN noncirrhotic); SOF+VEL (25 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection	Drug: SOF; SOF 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; Drug: VEL; Velpatasvir (VEL) tablet(s) administered orally once daily; Other Names: GS-5816
EXPERIMENTAL: Cohort 4,Group 2:SOF+VEL 25mg+RBV 8 wk (GT3 TN noncirrhotic); SOF+VEL(25 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: SOF; SOF 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; Drug: VEL; Velpatasvir (VEL) tablet(s) administered orally once daily; Other Names: GS-5816
EXPERIMENTAL: Cohort 4,Group 3: SOF+VEL 100mg 8 wk (GT3 TN noncirrhotic); SOF+VEL (100 mg) for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection	Drug: SOF; SOF 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; Drug: VEL; Velpatasvir (VEL) tablet(s) administered orally once daily; Other Names: GS-5816
EXPERIMENTAL: Cohort 4,Group 4: SOF+VEL 100mg+RBV 8 wk (GT3 TN noncirrhotic); SOF+VEL (100 mg)+RBV for 8 weeks in treatment-naive noncirrhotic participants with genotype 3 HCV infection	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: SOF; SOF 400 mg tablet administered orally once daily; Other Names: Sovaldi®; GS-7977; Drug: VEL; Velpatasvir (VEL) tablet(s) administered orally once daily; Other Names: GS-5816
EXPERIMENTAL: Cohort 5,Group 1: LDV/SOF + RBV 24 wk (SOF retreatment); LDV/SOF+RBV for 24 weeks in participants with genotype 1, 2, 3, or 6 HCV infection and who failed to achieve SVR in a previous Gilead sofosbuvir study	Drug: RBV; Ribavirin (RBV) 200 mg tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg); Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
EXPERIMENTAL: Cohort 6,Group 1: LDV/SOF 12 wk (GT1, HBV coinfection); LDV/SOF for 12 weeks in participants with genotype 1 HCV and hepatitis B virus (HBV) coinfection	Drug: LDV/SOF; Ledipasvir/sofosbuvir (LDV/SOF) (90 /400 mg) fixed-dose combination (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 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 is defined as HCV RNA < lower limit of quantification (LLOQ) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Percentage of Participants With Adverse Events Leading to Permanent Discontinuation of Study Drug(s)		Up to 24 weeks plus 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Viral Relapse	Viral relapse is defined as 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.	Up to Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment		Weeks 1 and 2
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment		Weeks 4, 6, and 8
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment		Week 10
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment		Week 12
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment		Weeks 16, 20, and 24
Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR 24)		Posttreatment Weeks 2, 4, 8, and 24
For Cohort 6, Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 16 and 20 Weeks After Discontinuation of Therapy (SVR16 and SVR 20)		Posttreatment Weeks 16 and 20
Percentage of Participants With On-treatment Virologic Failure	On-treatment virologic failure was defined as: 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)	Up to Posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Gane EJ, Hyland RH, An D, Svarovskaia E, Pang PS, Brainard D, Stedman CA. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology. 2015 Nov;149(6):1454-1461.e1. doi: 10.1053/j.gastro.2015.07.063. Epub 2015 Aug 7.
• Gane EJ, Hyland RH, An D, Svarovskaia ES, Brainard D, McHutchison JG. Ledipasvir and sofosbuvir for HCV infection in patients coinfected with HBV. Antivir Ther. 2016;21(7):605-609. doi: 10.3851/IMP3066. Epub 2016 Jul 1.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): March 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 4, 2013
• First Posted (ESTIMATE): April 9, 2013

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: September 1, 2016

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; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: GS-US-337-0122

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