Hepatitis C Virus Infection
Conditions
Keywords
Veterans HCV
Brief summary
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.
Interventions
DRUGSofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
DRUGRBV
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)
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: * Eligible for treatment with interferon (IFN)-based therapy * Ineligible for IFN treatment * Intolerant to IFN. * 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
* Current participation in an interventional clinical trial. * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV). * History of any other clinically significant chronic liver disease (e.g., hemochromatosis; Wilson's disease; α1-antitrypsin deficiency), except nonalcoholic steatohepatitis (NASH). * Decompensated liver * History of hemoglobinopathies * Contraindication or hypersensitivity to RBV * History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the participation for the full duration of the study, such that it is not in the best interest of the individual to participate. * Clinically significant ECG abnormality at screening. * History of solid organ transplantation. * Presence of hepatocellular carcinoma (HCC) Malignancy within 5 years prior to screening, with the exception of specific cancers that are entirely cured by surgical resection (basal cell skin cancer and prostate cancer in remission). Individuals under evaluation for possible malignancy are not eligible. * Prior treatment with an NS5B polymerase inhibitor. * Chronic use of systemic immunosuppressive agents or immunomodulatory agents (e.g., prednisone equivalent \> 10 mg/day). * Concomitant disallowed as per the Sovaldi Packet Insert. * Known hypersensitivity to the study drug, the metabolites, or formulation excipient. * History of difficulty with blood collection and/or poor venous access for the purposes of phlebotomy. * Use of any prohibited concomitant medications as described in the study protocol * Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug. * Male with pregnant female partner. * In the judgment of the investigator any clinically-relevant drug or alcohol abuse within 12 months of screening that may interfere with treatment, assessment or compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. |
| Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | Up to 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4) | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ at 4 weeks following the last dose of study drug. |
| Percentage of Participants Experiencing Viral Breakthrough | Up to Posttreatment Weak 12 | Viral breakthrough was defined as either: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment * HCV RNA ≥ LLOQ at the last available on-treatment measurement with no subsequent follow-up values |
| Percentage of Participants Experiencing Viral Relapse | Up to Posttreatment Week 12 | Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA \< LLOQ at end of treatment. |
| Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | Pretreatment and Posttreatment Week 12 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
113 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 47 |
| 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. | 19 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | SOF+RBV 12 Weeks (TE) | Total | SOF+RBV 12 Weeks (TN) |
|---|---|---|---|
| Age, Continuous | 62 Years STANDARD_DEVIATION 5.4 | 63 Years STANDARD_DEVIATION 5.8 | 64 Years STANDARD_DEVIATION 6 |
| Cirrhosis Status No | 0 participants | 0 participants | 0 participants |
| Cirrhosis Status Yes | 19 participants | 66 participants | 47 participants |
| HCV Genotype Genotype 2 | 2 participants | 4 participants | 2 participants |
| HCV Genotype Genotype 2a/2c | 0 participants | 8 participants | 8 participants |
| HCV Genotype Genotype 2b | 17 participants | 54 participants | 37 participants |
| HCV RNA | 6.6 log10 IU/mL STANDARD_DEVIATION 0.48 | 6.1 log10 IU/mL STANDARD_DEVIATION 0.87 | 5.9 log10 IU/mL STANDARD_DEVIATION 0.89 |
| HCV RNA Category < 800,000 IU/mL | 2 participants | 23 participants | 21 participants |
| HCV RNA Category ≥ 800,000 IU/mL | 17 participants | 43 participants | 26 participants |
| IL28b Status CC | 8 participants | 33 participants | 25 participants |
| IL28b Status CT | 10 participants | 29 participants | 19 participants |
| IL28b Status TT | 1 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants | 10 participants | 8 participants |
| Race/Ethnicity, Customized Hawaiian or Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 17 participants | 54 participants | 37 participants |
| Region of Enrollment United States | 19 participants | 66 participants | 47 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 66 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 66 |
| serious Total, serious adverse events | 8 / 66 |
Outcome results
Primary
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks (TN) | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event | 4.5 Percentage of participants |
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.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks (TN) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy | 76.6 Percentage of participants |
| SOF+RBV 12 Weeks (TE) | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy | 84.2 Percentage of participants |
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.
Time frame: Pretreatment and Posttreatment Week 12
Population: Participants who relapsed and qualified for sequencing analysis were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SOF+RBV 12 Weeks (TN) | Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | NS5B NI RAV Pretreatment | 2 participants |
| SOF+RBV 12 Weeks (TN) | Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | NS5B NI RAV Posttreatment | 5 participants |
| SOF+RBV 12 Weeks (TN) | Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | NS5B RBV RAV Pretreatment | 0 participants |
| SOF+RBV 12 Weeks (TN) | Number of Participants With Nonstructural Protein 5B (NS5B) Nucleoside Inhibitor (NI) Resistance-Associated Variants (RAVs) and RBV RAVs at Pretreatment and Posttreatment | NS5B RBV RAV Posttreatment | 0 participants |
Secondary
Percentage of Participants Experiencing Viral Breakthrough
Viral breakthrough was defined as either: * HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment * HCV RNA ≥ LLOQ at the last available on-treatment measurement with no subsequent follow-up values
Time frame: Up to Posttreatment Weak 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks (TN) | Percentage of Participants Experiencing Viral Breakthrough | 0 Percentage of participants |
| SOF+RBV 12 Weeks (TE) | Percentage of Participants Experiencing Viral Breakthrough | 0 Percentage of participants |
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.
Time frame: Up to Posttreatment Week 12
Population: Participants in the Full Analysis Set with available data were analyzed~.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks (TN) | Percentage of Participants Experiencing Viral Relapse | 17.4 Percentage of participants |
| SOF+RBV 12 Weeks (TE) | Percentage of Participants Experiencing Viral Relapse | 15.8 Percentage of participants |
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.
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SOF+RBV 12 Weeks (TN) | Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4) | 78.7 percentage of participants |
| SOF+RBV 12 Weeks (TE) | Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4) | 89.5 percentage of participants |