Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection (ION-2)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

ClinicalTrials.gov Identifier:

NCT01768286

First received: January 10, 2013

Last updated: November 21, 2014

Last verified: November 2014

History of Changes

Results First Received: November 21, 2014

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: 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 a total of 64 study sites in the United States. The first participant was screened on 03 January 2013. The last participant observation occurred on 20 February 2014.

Pre-Assignment Details

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

Reporting Groups

	Description
LDV/SOF 12 Weeks	Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet once daily for 12 weeks
LDV/SOF+RBV 12 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus ribavirin (RBV) tablets (1000-1200 mg daily based on weight) for 12 weeks
LDV/SOF 24 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks
LDV/SOF+RBV 24 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks

Participant Flow: Overall Study

	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
STARTED	109	111	110	111
COMPLETED	102	107	108	110
NOT COMPLETED	7	4	2	1
Randomized But Not Treated	0	0	1	0
Lack of Efficacy	7	4	0	1
Withdrew Consent	0	0	1	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 were randomized and received at least one dose of study drug. Participants failed a previous HCV treatment regimen consisting of pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (Pegintron) plus ribavirin (RBV), with or without a protease inhibitor (PI).

Reporting Groups

	Description
LDV/SOF 12 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
LDV/SOF+RBV 12 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks
LDV/SOF 24 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks
LDV/SOF+RBV 24 Weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Total	Total of all reporting groups

Baseline Measures

	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks	Total
Number of Participants [units: participants]	109	111	109	111	440
Age [units: years] Mean (Standard Deviation)	56 (6.9)	57 (8.0)	56 (8.3)	55 (7.8)	56 (7.8)
Gender [units: participants]
Female	35	40	35	43	153
Male	74	71	74	68	287
Race/Ethnicity, Customized [units: participants]
Black or African American	24	16	17	20	77
White	84	94	91	89	358
Asian	1	0	0	0	1
Hawaiian or Pacific Islander	0	1	0	1	2
Other	0	0	1	1	2
Race/Ethnicity, Customized [units: participants]
Hispanic/Latino	7	12	11	11	41
Not Hispanic or Latino	100	99	98	99	396
Not Disclosed	2	0	0	1	3
HCV RNA [units: log10 IU/mL] Mean (Standard Deviation)	6.5 (0.44)	6.4 (0.54)	6.4 (0.57)	6.5 (0.60)	6.5 (0.54)
HCV RNA Category [units: participants]
< 800,000 IU/mL	6	13	16	15	50
≥ 800,000 IU/mL	103	98	93	96	390
HCV Genotype [units: participants]
Genotype 1a	86	88	85	88	347
Genotype 1b	23	23	24	23	93
IL28b Status ^[1] [units: participants]
CC	10	11	16	18	55
CT	70	77	68	68	283
TT	29	23	25	25	102
Prior HCV Treatment ^[2] [units: participants]
PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV	43	47	58	59	207
PI+PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV	66	64	50	51	231
IFN-alfa-2b+RBV	0	0	1	1	2

[1]	CC, CT, and TT alleles are different forms of the IL28b gene.
[2]	IFN-alfa-2b = interferon-alfa 2b; PEG-IFN-alfa-2a = pegylated interferon alfa-2a; PEG-IFN-alfa-2b - pegylated interferon alfa-2b; RBV = ribavirin; PI = protease inhibitor

Outcome Measures

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1. Primary:

Percentage of Participants With Sustained Virologic Response (SVR) 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 From Any Study Drug [ Time Frame: Up to 24 weeks ]

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3. Secondary:

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]

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4. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ]

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5. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ]

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6. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ]

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7. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ]

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8. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ]

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9. Secondary:

Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ]

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10. Secondary:

Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ]

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11. Secondary:

Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ]

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12. Secondary:

Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ]

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13. Secondary:

Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ]

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14. Secondary:

Percentage of Participants With Virologic Failure [ 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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More Information

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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):

Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01768286 History of Changes
Other Study ID Numbers:	GS-US-337-0109
Study First Received:	January 10, 2013
Results First Received:	November 21, 2014
Last Updated:	November 21, 2014
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

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