Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection (ION-2)
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| ClinicalTrials.gov Identifier: NCT01768286 |
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Recruitment Status :
Completed
First Posted : January 15, 2013
Results First Posted : November 26, 2014
Last Update Posted : November 16, 2018
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Sponsor:
Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Hepatitis C Virus | Drug: LDV/SOF Drug: RBV | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 441 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Study Start Date : | January 2013 |
| Actual Primary Completion Date : | November 2013 |
| Actual Study Completion Date : | February 2014 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: LDV/SOF 12 Weeks
Participants will receive LDV/SOF FDC for 12 weeks.
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Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Names:
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Experimental: LDV/SOF+RBV 12 Weeks
Participants will receive LDV/SOF FDC plus RBV for 12 weeks.
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Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Names:
Drug: 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) |
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Experimental: LDV/SOF 24 Weeks
Participants will receive LDV/SOF FDC for 24 weeks.
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Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Names:
|
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Experimental: LDV/SOF+RBV 24 Weeks
Participants will receive LDV/SOF FDC plus RBV for 24 weeks.
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Drug: LDV/SOF
Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Names:
Drug: 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) |
Primary Outcome Measures :
- Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]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.
- Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug [ Time Frame: Up to 24 weeks ]The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
Secondary Outcome Measures :
- Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
- Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ]
- Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ]
- Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ]
- Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ]
- Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ]
- Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ]
- Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ]
- Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ]
- Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ]
- Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ]
- Percentage of Participants With Virologic Failure [ Time Frame: Baseline to posttreatment Week 24 ]
Virologic failure was defined as on-treatment virologic failure or virologic relapse.
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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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01768286
Locations
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Sponsors and Collaborators
Gilead Sciences
Investigators
| Study Director: | Jenny Yang, PharmD | Gilead Sciences |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Gilead Sciences |
| ClinicalTrials.gov Identifier: | NCT01768286 |
| Other Study ID Numbers: |
GS-US-337-0109 |
| First Posted: | January 15, 2013 Key Record Dates |
| Results First Posted: | November 26, 2014 |
| Last Update Posted: | November 16, 2018 |
| Last Verified: | November 2014 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | 18 months after study completion |
| Access Criteria: | A secured external environment with username, password, and RSA code. |
| URL: | http://www.gilead.com/research/disclosure-and-transparency |
Keywords provided by Gilead Sciences:
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HCV genotype 1 (GT-1) HCV Sustained Virologic Response Direct Acting Antiviral Combination Therapy GS-7977 GS-5885 Ribavirin Open Label Sofosbuvir Additional relevant MeSH terms: Hepatitis Hepatitis, Chronic Hepatitis C Hepatitis C, Chronic |
Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action |
Additional relevant MeSH terms:
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Infections Hepatitis C Hepatitis C, Chronic Hepatitis Communicable Diseases Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases |
RNA Virus Infections Blood-Borne Infections Flaviviridae Infections Hepatitis, Chronic Ledipasvir, sofosbuvir drug combination Ledipasvir Antiviral Agents Anti-Infective Agents |