Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects - Full Text View

Purpose

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

Condition	Intervention	Phase
Chronic Hepatitis C Virus	Drug: LDV/SOF Drug: RBV	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Ribavirin Sofosbuvir

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after stopping study treatment.
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: No ]
The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.

Secondary Outcome Measures:

Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) [ Time Frame: Posttreatment Weeks 2, 4, 8, and 24 ] [ Designated as safety issue: No ]
SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA < LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively.
Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse [ Time Frame: Baseline to Posttreatment Week 24 ] [ Designated as safety issue: No ]
- Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.
- Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.


Enrollment:	100
Study Start Date:	October 2012
Study Completion Date:	January 2014
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LDV/SOF 8 Weeks (TN) Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks.	Drug: LDV/SOF LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily Other Name: Harvoni®
Experimental: LDV/SOF+RBV 8 Weeks (TN) Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks.	Drug: LDV/SOF LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily Other Name: Harvoni® Drug: RBV 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)
Experimental: LDV/SOF 12 Weeks (TN) Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks.	Drug: LDV/SOF LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily Other Name: Harvoni®
Experimental: LDV/SOF 12 Weeks (TE) Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor [PI]+pegylated interferon [PEG]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks.	Drug: LDV/SOF LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily Other Name: Harvoni®
Experimental: LDV/SOF+RBV 12 Weeks (TE) Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks.	Drug: LDV/SOF LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily Other Name: Harvoni® Drug: RBV 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)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age ≥ 18 years, with chronic genotype 1 HCV infection
HCV RNA equal to or greater than 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
Current or prior history of clinical hepatic decompensation
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 subject treatment, assessment or compliance with the protocol

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01726517

Locations


United States, Texas

San Antonio, Texas, United States, 78215

Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Rob Hyland	Gilead Sciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5. Erratum in: Lancet. 2014 Mar 8;383(9920):870.


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01726517 History of Changes
Other Study ID Numbers:	GS-US-337-0118
Study First Received:	November 10, 2012
Results First Received:	November 7, 2014
Last Updated:	November 7, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:


HCV genotype 1 (GT-1) HCV Sustained Virologic Response Direct Acting Antiviral Combination Therapy GS-7977 GS-5885	Ribavirin Open Label Sofosbuvir Treatment-Naïve Protease Inhibitors PI

Additional relevant MeSH terms:


Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections Hepatitis Liver Diseases	Digestive System Diseases Ribavirin Sofosbuvir Protease Inhibitors Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 29, 2016