Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection

Chronic Hepatitis C Virus Clinical Trial

— ION-2  

Official title:

A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin for 12 and 24 Weeks in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01768286
• Other study ID #: GS-US-337-0109
• Status: Completed
• Phase: Phase 3
• Start date: January 2013
• Est. completion date: February 2014

Study information

• Verified date: November 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (HCV) infection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 441
• Est. completion date: February 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18, with chronic genotype 1 HCV infection

• HCV treatment-experienced, including patients who have previously failed a nonstructural protein (NS)3/4A protease inhibitor plus pegylated interferon (PEG)/RBV regimen

• HCV RNA > 10,000 IU/mL at screening

• 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

• Coinfection with HIV or hepatitis B virus

• Current or prior history of clinical hepatic decompensation

• Hepatocellular carcinoma 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 subject treatment, assessment or compliance with the protocol

Related Conditions & MeSH terms

• Chronic Hepatitis C Virus
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
• RBV
Ribavirin (RBV) 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

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 quantitation (LLOQ; ie, 25 IU/mL) 12 weeks following the last dose of study drug.	Posttreatment Week 12
Primary	Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug	The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.	Up to 24 weeks
Secondary	Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.	Posttreatment Weeks 4 and 24
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 1		Week 1
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 2		Week 2
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 4		Week 4
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 8		Week 8
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 12		Week 12
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 24		Week 24
Secondary	Change From Baseline in HCV RNA at Week 1		Baseline; Week 1
Secondary	Change From Baseline in HCV RNA at Week 2		Baseline; Week 2
Secondary	Change From Baseline in HCV RNA at Week 4		Baseline; Week 4
Secondary	Change From Baseline in HCV RNA at Week 8		Baseline; Week 8
Secondary	Percentage of Participants With Virologic Failure	Virologic failure was defined as on-treatment virologic failure or virologic relapse.; 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); Virologic relapse was defined as confirmed HCV RNA = LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.	Baseline to posttreatment Week 24