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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition:	Chronic Hepatitis C Virus
Interventions:	Drug: LDV/SOF; Drug: RBV

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled at 1 study site in the United States. The first participant was screened on 22 October 2012. The last participant observation was on 13 January 2014.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
116 participants were screened.

Reporting Groups

	Description
LDV/SOF 8 Weeks (TN)	Treatment-naive (TN) participants were randomized to receive ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg for 8 weeks.
LDV/SOF+RBV 8 Weeks (TN)	Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based ribavirin (RBV) (1000-1200 mg) for 8 weeks.
LDV/SOF 12 Weeks (TN)	Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks.
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) were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks.
LDV/SOF+RBV 12 Weeks (TE)	Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based RBV (1000-1200 mg) for 12 weeks.

Participant Flow:   Overall Study

	LDV/SOF 8 Weeks (TN)	LDV/SOF+RBV 8 Weeks (TN)	LDV/SOF 12 Weeks (TN)	LDV/SOF 12 Weeks (TE)	LDV/SOF+RBV 12 Weeks (TE)
STARTED	20	21	19	19	21
COMPLETED	20	21	18	19	21
NOT COMPLETED	0	0	1	0	0
Withdrawal by Subject	0	0	1	0	0

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set: participants received at least 1 dose of study drug

Reporting Groups

	Description
LDV/SOF 8 Weeks (TN)	Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg for 8 weeks.
LDV/SOF+RBV 8 Weeks (TN)	Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based RBV (1000-1200 mg) for 8 weeks.
LDV/SOF 12 Weeks (TN)	Treatment-naive participants were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks.
LDV/SOF 12 Weeks (TE)	Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) were randomized to receive LDV 90 mg/SOF 400 mg for 12 weeks.
LDV/SOF+RBV 12 Weeks (TE)	Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) were randomized to receive LDV 90 mg/SOF 400 mg plus weight-based RBV (1000-1200 mg) for 12 weeks.
Total	Total of all reporting groups

Baseline Measures

	LDV/SOF 8 Weeks (TN)	LDV/SOF+RBV 8 Weeks (TN)	LDV/SOF 12 Weeks (TN)	LDV/SOF 12 Weeks (TE)	LDV/SOF+RBV 12 Weeks (TE)	Total
Overall Participants Analyzed; [Units: Participants]	20	21	19	19	21	100
Age; [Units: Years]; Mean (Standard Deviation)	48 (10.7)	50 (11.1)	46 (11.6)	54 (6.6)	52 (9.8)	50 (10.4)
Gender; [Units: Participants]
Female	6	9	8	4	7	34
Male	14	12	11	15	14	66
Ethnicity (NIH/OMB); [Units: Participants]
Hispanic or Latino	3	12	9	6	10	40
Not Hispanic or Latino	17	9	10	13	11	60
Unknown or Not Reported	0	0	0	0	0	0
Race (NIH/OMB); [Units: Participants]
American Indian or Alaska Native	0	0	0	1	0	1
Asian	1	0	1	0	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	4	0	1	2	2	9
White	15	21	17	16	19	88
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0
Hepatitis C Virus (HCV) Genotype [1]; [Units: Participants]
1a	17	19	17	18	16	87
1b	3	2	2	1	5	13
[1] There are variations within HCV genotype 1 which are distinct enough to be referred to as genotypes 1a or 1b.
IL28b Status [1]; [Units: Participants]
CC	4	7	1	2	1	15
CT	12	11	14	13	11	61
TT	4	3	4	4	9	24
[1] CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA (log10 IU/mL); [Units: Log10 IU/mL]; Mean (Standard Deviation)	6.1 (0.82)	6.0 (0.84)	6.1 (0.79)	6.3 (0.49)	6.2 (0.42)	6.1 (0.69)
HCV RNA Category; [Units: Participants]
< 800,000 IU/mL	9	7	7	4	5	32
≥ 800,000 IU/mL	11	14	12	15	16	68
Prior HCV Treatment and Response [1]; [Units: Participants]
Non-responder to PI boceprevir	0	0	0	9	9	18
Relapse/Breakthrough to PI boceprevir	0	0	0	2	2	4
Non-responder to PI telaprevir	0	0	0	3	6	9
Relapse/Breakthrough to PI telaprevir	0	0	0	5	4	9
[1] Prior HCV treatment and response was only collected for treatment-experienced participants in the LDV/SOF 12 Weeks (TE) and LDV/SOF+RBV 12 Weeks (TE) groups.
Cirrhosis; [Units: Participants]
No	20	21	19	8	10	78
Yes	0	0	0	11	11	22

  Outcome Measures

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1. Primary:

Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]

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2. Primary:

Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Baseline to Week 12 ]

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3. Secondary:

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 ]

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4. Secondary:

Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse [ Time Frame: Baseline to Posttreatment Week 24 ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or; The study has been completed at all study sites for at least 2 years

Results Point of Contact:  

Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com

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
First Submitted:	November 10, 2012
First Posted:	November 15, 2012
Results First Submitted:	November 7, 2014
Results First Posted:	November 17, 2014
Last Update Posted:	November 17, 2014