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The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LDV/SOF GT 1 or 4 | Experimental | Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks. |
|
| SOF+RBV 12 wks GT 2 | Experimental | Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks. |
|
| SOF+RBV 24 wks GT 3 | Experimental | Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LDV/SOF | Drug | 90/400 mg FDC tablet administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. | Posttreatment Week 12 |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Posttreatment Week 4 |
| Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |
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Inclusion Criteria:
Hemophilia A, B or C, or Von Willebrand's disease
Chronic genotype 1, 2, 3 or 4 HCV infection
HCV RNA ≥ 1000 IU/mL at screening
Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
Screening laboratory values within defined thresholds
For HIV-1/HCV co-infected individuals:
Exclusion Criteria:
Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
Current or prior history of any of the following:
Pregnant or nursing female
Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
Chronic use of systemically administered immunosuppressive agents
For HIV-1/HCV co-infected individuals:
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| Name | Affiliation | Role |
|---|---|---|
| Robert H Hyland, DPhil | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sacramento | California | 95817 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Walsh C, Workowski K, Terrault N, Sax S, Cohen A, et al. Approved All-Oral Sofosbuvir Regimens Are Safe and Highly Effective in Patients With Hereditary Bleeding Disorders. (2015). Hepatology, 62 (S1): 714A-807A. doi:10.1002/hep.28228 |
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147 participants were screened.
Participants were enrolled at study sites in the United States. The first participant was screened on 10 April 2014. The last study visit occurred on 17 August 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | LDV/SOF 12 Weeks GT1 or GT4 | Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks (genotype 1 or 4) |
| FG001 | LDV/SOF 24 Weeks GT1 (TE) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| SOF | Drug | 400 mg tablet administered orally once daily |
|
|
| 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) |
|
| Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |
| Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 | Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |
| Percentage of Participants With Virologic Failure | Virologic failure was defined as:
| Up to Posttreatment Week 24 |
| Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only) | Weeks 4, 8, 12, 16, 20, and 24 |
| Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only) | Baseline; Weeks 12, 24, and Posttreatment Week 12 |
| San Diego |
| California |
| 92103-8651 |
| United States |
| San Francisco | California | 94143 | United States |
| Washington D.C. | District of Columbia | 20007 | United States |
| Atlanta | Georgia | 30308 | United States |
| Boston | Massachusetts | 02114 | United States |
| Boston | Massachusetts | 02115 | United States |
| Minneapolis | Minnesota | 55407 | United States |
| Newark | New Jersey | 07112 | United States |
| New York | New York | 10029 | United States |
| Rochester | New York | 14621 | United States |
| Chapel Hill | North Carolina | 27599-7584 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
LDV/SOF (90/400 mg) FDC tablet once daily for 24 weeks (treatment-experienced [TE] participants with genotype 1 HCV infection and cirrhosis)
| FG002 | SOF+RBV 12 Weeks GT2 | Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 2) |
| FG003 | SOF+RBV 24 Weeks GT3 | SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks (genotype 3) |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety Analysis Set: participants who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | LDV/SOF 12 Weeks GT1 or GT4 | Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks (genotype 1 or 4) |
| BG001 | LDV/SOF 24 Weeks GT1 (TE) | LDV/SOF (90/400 mg) FDC tablet once daily for 24 weeks (treatment-experienced [TE] participants with genotype 1 HCV infection and cirrhosis) |
| BG002 | SOF+RBV 12 Weeks GT2 | Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 2) |
| BG003 | SOF+RBV 24 Weeks GT3 | SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks (genotype 3) |
| BG004 | 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 | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Cirrhosis Status | Number | participants |
| ||||||||||||||||
| HCV Genotype | Number | participants |
| ||||||||||||||||
| HCV RNA | Mean | Standard Deviation | log10 IU/mL |
| |||||||||||||||
| HCV RNA Category | Number | participants |
| ||||||||||||||||
| IL28b Status | CC, CT, and TT alleles are different forms of the IL28b gene. | Number | participants |
| |||||||||||||||
| HIV Status | 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 (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. | Full Analysis Set: participants enrolled into the study and received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | Posttreatment Week 12 |
|
|
| ||||||||||||||||||||||||||||||||||
| Primary | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Safety Analysis Set | Posted | Number | percentage of participants | Up to 24 weeks |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment. | Full Analysis Set | Posted | Number | 95% Confidence Interval | percentage of participants | Posttreatment Week 4 |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 | Participants in the Full Analysis Set with available data were analyzed. | Posted | Number | percentage of participants | Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 | Participants in the Full Analysis Set with available data were analyzed. | Posted | Mean | Standard Deviation | log10 IU/mL | Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Virologic Failure | Virologic failure was defined as:
| Full Analysis Set | Posted | Number | percentage of participants | Up to Posttreatment Week 24 |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only) | Only the participants coinfected with HIV-1 and HCV in the Safety Analysis Set with available data were analyzed. | Posted | Number | percentage of participants | Weeks 4, 8, 12, 16, 20, and 24 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only) | Participants coinfected with HIV-1 and HCV in the Safety Analysis Set with available data were analyzed. | Posted | Mean | Standard Deviation | mg/dL | Baseline; Weeks 12, 24, and Posttreatment Week 12 |
|
|
Up to 24 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 12 Weeks GT1 or GT4 | Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily for 12 weeks (genotype 1 or 4) | 5 | 99 | 54 | 99 | ||
| EG001 | LDV/SOF 24 Weeks GT1 (TE) | LDV/SOF (90/400 mg) FDC tablet once daily for 24 weeks (treatment-experienced [TE] participants with genotype 1 HCV infection and cirrhosis) | 0 | 5 | 3 | 5 | ||
| EG002 | SOF+RBV 12 Weeks GT2 | Sofosbuvir (SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 2) | 0 | 10 | 8 | 10 | ||
| EG003 | SOF+RBV 24 Weeks GT3 | SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks (genotype 3) | 1 | 6 | 4 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Miscarriage of partner | Social circumstances | MedDRA Version 18.0. | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA Version 18.0. | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 18.0. | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA Version 18.0. | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 18.0. | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA Version 18.0. | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Haemarthrosis | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Osteorrhagia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 18.0. | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Mood altered | Psychiatric disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 18.0. | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA Version 18.0. | Systematic Assessment |
|
There were no limitations affecting the analysis or results.
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 | ClinicalTrialDisclosures@gilead.com |
| ID | Term |
|---|---|
| C000595958 | ledipasvir, sofosbuvir drug combination |
| D000069474 | Sofosbuvir |
| ID | Term |
|---|---|
| D014542 | Uridine Monophosphate |
| D014500 | Uracil Nucleotides |
| D011742 | Pyrimidine Nucleotides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| White |
|
| Asian |
|
| Other |
|
| Yes |
|
| Genotype 2 |
|
| Genotype 3 |
|
| Genotype 4 |
|
| ≥ 800,000 IU/mL |
|
| CT |
|
| TT |
|
| Positive |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| OG003 | SOF+RBV 24 Weeks GT3 | SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks (genotype 3) |
|
|
|
|