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This study will examine the safety, tolerability, and antiviral efficacy of sofosbuvir (SOF)+ribavirin (RBV) in treatment-naive and treatment-experienced United States Veterans with compensated cirrhosis and genotype 2 HCV infection.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sofosbuvir+RBV 12 weeks | Experimental | Participants will receive sofosbuvir+RBV for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sofosbuvir | Drug | Sofosbuvir 400 mg tablet administered orally once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 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 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug. | Posttreatment Week 4 |
| Percentage of Participants Experiencing Viral Breakthrough |
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Inclusion Criteria:
Willing and able to provide written informed consent.
Treatment-naive or treatment-experienced adult, U.S. Veteran
Chronic genotype 2 (GT2) HCV infection Classified as:
Cirrhosis determination
Laboratory parameters within prespecified ranges at screening:
A negative serum pregnancy test is required for females of childbearing potential
Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Lactating females must agree to discontinue nursing before study drug is administered.
Males must agree to refrain from sperm donation from the date of screening until at least 7 months after the last dose of RBV, or 90 days after their last dose of study drug if not taking RBV.
Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.
Must be of generally good health as determined by the Investigator.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lorenzo Rossaro, MD | Gilead Sciences | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Beach | California | 90822 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27237429 | Result | Ho SB, Monto A, Peyton A, Kaplan DE, Byrne S, Moon S, Copans A, Rossaro L, Roy A, Le H, Dvory-Sobol H, Zhu Y, Brainard DM, Guyer W, Shaikh O, Fuchs M, Morgan TR; VALOR study team. Efficacy of Sofosbuvir Plus Ribavirin in Veterans With Hepatitis C Virus Genotype 2 Infection, Compensated Cirrhosis, and Multiple Comorbidities. Clin Gastroenterol Hepatol. 2017 Feb;15(2):282-288. doi: 10.1016/j.cgh.2016.05.024. Epub 2016 May 27. |
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113 participants were screened.
Participants were enrolled at a total of 15 study sites in the United States The first participant was screened on 04 June 2014. The last study visit occurred on 22 June 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | SOF+RBV 12 Weeks (TN) | Treatment-naive (TN) participants received sofosbuvir (Sovaldi®; SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks. |
| FG001 | SOF+RBV 12 Weeks (TE) |
| 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) |
|
Viral breakthrough was defined as either:
|
| Up to Posttreatment Weak 12 |
| Percentage of Participants Experiencing Viral Relapse | Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment. | Up to Posttreatment Week 12 |
| Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | Deep sequencing of the HCV NS5B gene was attempted for all participants who had virologic failure at pretreatment and posttreatment time points if the level of HCV RNA in the plasma sample was ≥ 1000 IU/L. | Pretreatment and Posttreatment Week 12 |
| Los Angeles |
| California |
| 90073 |
| United States |
| Palo Alto | California | 94394 | United States |
| San Diego | California | 92102 | United States |
| San Francisco | California | 94121 | United States |
| New Haven | Connecticut | 06520 | United States |
| Miami | Florida | 33125 | United States |
| Decatur | Georgia | 30033 | United States |
| Baltimore | Maryland | 21201 | United States |
| Kansas City | Missouri | 64128 | United States |
| Durham | North Carolina | 27705 | United States |
| Portland | Oregon | 97239 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
| Pittsburgh | Pennsylvania | 15240 | United States |
| Dallas | Texas | 75216 | United States |
| Houston | Texas | 77030 | United States |
| Richmond | Virginia | 23249 | United States |
Treatment-experienced participants received sofosbuvir (Sovaldi®; SOF) 400 mg tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
| COMPLETED |
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| NOT COMPLETED |
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Safety analysis set: participants who received at least 1 dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | SOF+RBV 12 Weeks (TN) | Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks. |
| BG001 | SOF+RBV 12 Weeks (TE) | Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks. |
| BG002 | 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 |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| IL28b Status | Number | participants |
| ||||||||||||||||
| HCV RNA | Mean | Standard Deviation | log10 IU/mL |
| |||||||||||||||
| HCV RNA Category | Number | participants |
| ||||||||||||||||
| HCV Genotype | Number | participants |
| ||||||||||||||||
| Cirrhosis Status | Number | participants |
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| 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 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. | Full Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug | Posted | Number | 95% Confidence Interval | Percentage of participants | Posttreatment Week 12 |
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| ||||||||||||||||||||||||||||
| Primary | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Safety Analysis Set: participants who received at least 1 dose of study drug | Posted | Number | Percentage of participants | Up to 12 weeks |
|
| |||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4) | SVR4 was defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug. | Full Analysis Set | Posted | Number | 95% Confidence Interval | percentage of participants | Posttreatment Week 4 |
|
| |||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Viral Breakthrough | Viral breakthrough was defined as either:
| Full Analysis Set | Posted | Number | Percentage of participants | Up to Posttreatment Weak 12 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Experiencing Viral Relapse | Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment. | Participants in the Full Analysis Set with available data were analyzed . | Posted | Number | Percentage of participants | Up to Posttreatment Week 12 |
|
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | Deep sequencing of the HCV NS5B gene was attempted for all participants who had virologic failure at pretreatment and posttreatment time points if the level of HCV RNA in the plasma sample was ≥ 1000 IU/L. | Participants who relapsed and qualified for sequencing analysis were analyzed. | Posted | Number | participants | Pretreatment and Posttreatment Week 12 |
|
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Up to12 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 | SOF+RBV 12 Weeks (All Participants) | SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks. | 8 | 66 | 45 | 66 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Oesophageal varices haemorrhage | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA Version 18.0 | Systematic Assessment |
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| Endocarditis staphylococcal | Infections and infestations | MedDRA Version 18.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA Version 18.0 | Systematic Assessment |
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| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Drug withdrawal convulsions | Nervous system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 18.0 | Systematic Assessment |
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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 |
|---|---|
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| 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 |
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| Male |
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| White |
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| Hawaiian or Pacific Islander |
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| Other |
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| CT |
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| TT |
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| ≥ 800,000 IU/mL |
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| Genotype 2b |
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| Genotype 2a/2c |
|
| Yes |
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