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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 in treatment-naive participants with chronic genotype 1 HCV infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LDV/SOF 8 Week | Experimental | Participants will receive LDV/SOF FDC for 8 weeks. |
|
| LDV/SOF+RBV 8 Week | Experimental | Participants will receive LDV/SOF FDC plus RBV for 8 weeks. |
|
| LDV/SOF 12 Week | Experimental | Participants will receive LDV/SOF FDC for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LDV/SOF | Drug | LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 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 |
| 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 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 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 |
| Percentage of Participants With HCV RNA < LLOQ at Week 2 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert H. Hyland, DPhil | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27553375 | Derived | Grebely J, Mauss S, Brown A, Bronowicki JP, Puoti M, Wyles D, Natha M, Zhu Y, Yang J, Kreter B, Brainard DM, Yun C, Carr V, Dore GJ. Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. Clin Infect Dis. 2016 Dec 1;63(11):1405-1411. doi: 10.1093/cid/ciw580. Epub 2016 Aug 23. | |
| 24720702 |
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Not provided
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.
18 months after study completion
A secured external environment with username, password, and RSA code.
831 participants were screened.
Participants were enrolled at a total of 59 study sites in the United States. The first participant was screened on 06 May 2013. The last participant observation occurred on 07 March 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | LDV/SOF 8 Week | Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet once daily for 8 weeks |
| FG001 | LDV/SOF+RBV 8 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily plus ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 8 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| RBV | Drug | 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) |
|
| Week 2 |
| Percentage of Participants With HCV RNA < LLOQ at Week 4 | Week 4 |
| Percentage of Participants With HCV RNA < LLOQ at Week 8 | Week 8 |
| Change From Baseline in HCV RNA at Week 2 | Baseline; Week 2 |
| Change From Baseline in HCV RNA at Week 4 | Baseline; Week 4 |
| Change From Baseline in HCV RNA at Week 8 | Baseline; Week 8 |
| Percentage of Participants Experiencing Virologic Failure | Virologic failure was defined as on-treatment virologic failure or virologic relapse.
| Baseline to posttreatment Week 24 |
| La Jolla |
| California |
| United States |
| Los Angeles | California | United States |
| Palo Alto | California | United States |
| Sacramento | California | United States |
| San Diego | California | United States |
| San Francisco | California | United States |
| Aurora | Colorado | United States |
| Englewood | Colorado | United States |
| Washington D.C. | District of Columbia | United States |
| Gainesville | Florida | United States |
| Jacksonville | Florida | United States |
| Miami | Florida | United States |
| Orlando | Florida | United States |
| Wellington | Florida | United States |
| Atlanta | Georgia | United States |
| Decatur | Georgia | United States |
| Marietta | Georgia | United States |
| Chicago | Illinois | United States |
| Indianapolis | Indiana | United States |
| Bowling Green | Kentucky | United States |
| Baton Rouge | Louisiana | United States |
| Baltimore | Maryland | United States |
| Lutherville | Maryland | United States |
| Boston | Massachusetts | United States |
| Novi | Michigan | United States |
| Kansas City | Missouri | United States |
| St Louis | Missouri | United States |
| Albuquerque | New Jersey | United States |
| Berlin | New Jersey | United States |
| Hillsborough | New Jersey | United States |
| Santa Fe | New Mexico | United States |
| Binghamton | New York | United States |
| Manhasset | New York | United States |
| New York | New York | United States |
| Chapel Hill | North Carolina | United States |
| Fayetteville | North Carolina | United States |
| Statesville | North Carolina | United States |
| Winston-Salem | North Carolina | United States |
| Philadelphia | Pennsylvania | United States |
| Providence | Rhode Island | United States |
| Germantown | Tennessee | United States |
| Nashville | Tennessee | United States |
| Arlington | Texas | United States |
| Houston | Texas | United States |
| San Antonio | Texas | United States |
| Fairfax | Virginia | United States |
| Falls Church | Virginia | United States |
| Newport News | Virginia | United States |
| Norfolk | Virginia | United States |
| Richmond | Virginia | United States |
| Seattle | Washington | United States |
| Derived |
| Kowdley KV, Gordon SC, Reddy KR, Rossaro L, Bernstein DE, Lawitz E, Shiffman ML, Schiff E, Ghalib R, Ryan M, Rustgi V, Chojkier M, Herring R, Di Bisceglie AM, Pockros PJ, Subramanian GM, An D, Svarovskaia E, Hyland RH, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Pound D, Fried MW; ION-3 Investigators. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med. 2014 May 15;370(20):1879-88. doi: 10.1056/NEJMoa1402355. Epub 2014 Apr 10. |
| FG002 | LDV/SOF 12 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Analysis Set: participants were randomized and received at least one dose of study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | LDV/SOF 8 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks |
| BG001 | LDV/SOF+RBV 8 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks |
| BG002 | LDV/SOF 12 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Gender was collected as "Sex at Birth." | Count of Participants | Participants |
| |||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| HCV RNA | Mean | Standard Deviation | log10 IU/mL |
| |||||||||||||||
| HCV RNA Category | Number | participants |
| ||||||||||||||||
| HCV Genotype | Number | participants |
| ||||||||||||||||
| IL28b Status | CC, CT, and TT alleles are different forms of the IL28b gene. | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Sustained Virologic Response 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. | Full Analysis Set: participants were randomized and received at least one dose of study medication. | Posted | Number | percentage of participants | Posttreatment Week 12 |
|
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | Safety Analysis Set | Posted | Number | percentage of participants | Up to 12 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Sustained Virologic Response 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. | Full Analysis Set | Posted | Number | percentage of participants | Posttreatment Weeks 4 and 24 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With HCV RNA < LLOQ at Week 2 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Number | percentage of participants | Week 2 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With HCV RNA < LLOQ at Week 4 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Number | percentage of participants | Week 4 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With HCV RNA < LLOQ at Week 8 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Number | percentage of participants | Week 8 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in HCV RNA at Week 2 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Mean | Standard Deviation | log10 IU/mL | Baseline; Week 2 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in HCV RNA at Week 4 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Mean | Standard Deviation | log10 IU/mL | Baseline; Week 4 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in HCV RNA at Week 8 | Participants in the Full Analysis Set with Available Data were analyzed. | Posted | Mean | Standard Deviation | log10 IU/mL | Baseline; Week 8 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Virologic Failure | Virologic failure was defined as on-treatment virologic failure or virologic relapse.
| Full Analysis Set | Posted | Number | percentage of participants | Baseline to posttreatment Week 24 |
|
Up to 12 weeks plus 30 days
Safety Analysis Set
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LDV/SOF 8 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks | 4 | 215 | 146 | 215 | ||
| EG001 | LDV/SOF+RBV 8 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks | 1 | 216 | 166 | 216 | ||
| EG002 | LDV/SOF 12 Week | LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks | 5 | 216 | 150 | 216 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Bile duct stone | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
| |
| Skeletal injury | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
| |
| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Pituitary tumour | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
| |
| Squamous cell carcinoma of lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Haemothorax 0 | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (16.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Irritability | General disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Systematic Assessment |
|
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:
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosures | Gilead Sciences, Inc. | ClinicalTrialDisclosures@gilead.com |
| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D006505 | Hepatitis |
| D006521 | Hepatitis, Chronic |
| D006526 | Hepatitis C |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D004769 | Enterovirus Infections |
| D010850 | Picornaviridae Infections |
| D012327 | RNA Virus Infections |
| D018178 | Flaviviridae Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000595958 | ledipasvir, sofosbuvir drug combination |
Not provided
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| Male |
|
| White |
|
| Asian |
|
| American Indian/Alaska Native |
|
| Hawaiian or Pacific Islander |
|
| Other |
|
| Not Disclosed |
|
| Not Hispanic or Latino |
|
| Not Disclosed |
|
| ≥ 800,000 IU/mL |
|
| Genotype 1a |
|
| Genotype 1b |
|
| CT |
|
| TT |
|
| <0.001 |
The p-value for the comparison of the LDV/SOF+RBV 8 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test. |
| 2-Sided |
| Superiority or Other |
| Binomial test | <0.001 | The p-value for the comparison of the LDV/SOF 12 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test. | 2-Sided | Superiority or Other |
| Difference in proportions | -3.2 | 2-Sided | 97.5 | -8.3 | 1.8 | Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions. | Non-Inferiority or Equivalence | Noninferiority would be demonstrated if the lower bound of the confidence interval (CI) for the difference between groups was greater than -12%. |
| Difference in proportions | -2.3 | 2-Sided | 97.5 | -7.2 | 2.5 | Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions. | Non-Inferiority or Equivalence | Noninferiority would be demonstrated if the lower bound of the CI for the difference between groups was greater than -12%. |
| Difference in proportions | 0.9 | 2-Sided | 95 | -3.9 | 5.7 | Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions. | Non-Inferiority or Equivalence | Noninferiority would be demonstrated if the lower bound of the CI for the difference between groups was greater than -12%. |
|
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| Units | Counts |
|---|---|
| Participants |
|
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