Chronic Hepatitis C
Conditions
Keywords
HCV genotype 1 (GT-1), HCV genotype 4 (GT-4), HCV genotype 5 (GT-5), HCV genotype 6 (GT-6), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Treatment-Naïve, GS-7977, Ribavirin, RBV, Peginterferon Alfa 2a, PEG
Brief summary
This study was to assess whether sofosbuvir in combination with ribavirin (RBV) and pegylated interferon alfa 2a (PEG) administered for 12 weeks is safe and effective in patients with hepatitis C virus (HCV) genotypes 1, 4, 5 , or 6 as assessed by the rate of sustained viral response (SVR) 12 weeks after discontinuation of therapy (SVR12).
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 (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
DRUGPEG
Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
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
* Infection with HCV genotype 1, 4, 5, or 6 * Cirrhosis determination * Subject met the following classifications: * Treatment-naive * Screening laboratory values within defined thresholds * Not treated with any investigational drug or device within 30 days of screening * Use of highly effective contraception methods if female of childbearing potential or sexually active male
Exclusion criteria
* Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase * Pregnant or nursing female, or male with pregnant female partner * Current or prior history of clinical hepatic decompensation * History of clinically-significant illness or any other major medical disorder that may have interfered with subject treatment, assessment, or compliance with the protocol * Excessive alcohol ingestion or significant drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response (SVR)12 | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after cessation of therapy. |
| Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Baseline to Week 12 | The number of participants experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. Participants discontinuing study drug were permitted to remain on the study for further assessments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving SVR4 | Posttreatment Week 4 | SVR4 was defined as HCV RNA \< LLOQ 4 weeks after cessation of therapy |
| Percentage of Participants Achieving SVR24 | Posttreatment Week 24 | SVR24 was defined as HCV RNA \< LLOQ 24 weeks after cessation of therapy |
| Percentage of Participants With Viral Breakthrough | Baseline to Week 12 | Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values. |
| Percentage of Participants With Viral Relapse | End of treatment to post-treatment Week 24 | Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Subjects were enrolled in a total of 55 study sites in the United States. The first participant was screened on 18 June 2012. The last participant observation was on 16 April 2013.
Pre-assignment details
456 participants were screened and 328 were enrolled; 327 participants were treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| Sofosbuvir+PEG+RBV Participants received Sofosbuvir+PEG+RBV for 12 weeks and were followed for 24 weeks following treatment.
Sofosbuvir (400 mg) was administered as an oral tablet, PEG (180 µg) as a subcutaneous injection, and RBV (1000-1200 mg) as 200 mg oral tablets. | 327 |
| Total | 327 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Efficacy failure | 29 |
| Overall Study | Enrolled but not treated | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Sofosbuvir+PEG+RBV |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 281 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HCV RNA | 6.4 log10 IU/mL STANDARD_DEVIATION 0.67 |
| HCV RNA Category < 6 log10 IU/mL | 71 participants |
| HCV RNA Category ≥ 6 log10 IU/mL | 256 participants |
| Hepatitis C Virus (HCV) genotype Genotype 1a | 225 participants |
| Hepatitis C Virus (HCV) genotype Genotype 1a/1b | 1 participants |
| Hepatitis C Virus (HCV) genotype Genotype 1b | 66 participants |
| Hepatitis C Virus (HCV) genotype Genotype 4 | 28 participants |
| Hepatitis C Virus (HCV) genotype Genotype 5 | 1 participants |
| Hepatitis C Virus (HCV) genotype Genotype 6 | 6 participants |
| IL28 Genotype CC | 95 participants |
| IL28 Genotype CT | 181 participants |
| IL28 Genotype TT | 51 participants |
| Race/Ethnicity, Customized American Indian/ Alaska Native/ First Nations | 6 participants |
| Race/Ethnicity, Customized Asian | 7 participants |
| Race/Ethnicity, Customized Black or African American | 54 participants |
| Race/Ethnicity, Customized Hawaiian or Pacific Islander | 2 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 257 participants |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 209 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 310 / 327 |
| serious Total, serious adverse events | 4 / 327 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug
The number of participants experiencing adverse events leading to permanent discontinuation of study drug was summarized. Adverse events may or may not have been related to study treatment. Participants discontinuing study drug were permitted to remain on the study for further assessments.
Time frame: Baseline to Week 12
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Anaemia | 2 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Haemolytic anaemia | 1 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Neutropenia | 1 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Vision blurred | 1 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Blood creatinine increased | 1 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Haemoglobin abnormal | 1 participants |
| Sofosbuvir+PEG+RBV | Number of Participants Experiencing Adverse Events Leading to Permanent Discontinuation of Study Drug | Dermatitis | 1 participants |
Primary
Percentage of Participants Achieving Sustained Virologic Response (SVR)12
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after cessation of therapy.
Time frame: Posttreatment Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sofosbuvir+PEG+RBV | Percentage of Participants Achieving Sustained Virologic Response (SVR)12 | 91 percentage of participants |
Comparison: Superiority would be demonstrated if the SVR12 rate was higher than the 60% null SVR rate based on historical control data.p-value: <0.001Binomial exact test
Secondary
Percentage of Participants Achieving SVR24
SVR24 was defined as HCV RNA \< LLOQ 24 weeks after cessation of therapy
Time frame: Posttreatment Week 24
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sofosbuvir+PEG+RBV | Percentage of Participants Achieving SVR24 | 90.5 percentage of participants |
Secondary
Percentage of Participants Achieving SVR4
SVR4 was defined as HCV RNA \< LLOQ 4 weeks after cessation of therapy
Time frame: Posttreatment Week 4
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sofosbuvir+PEG+RBV | Percentage of Participants Achieving SVR4 | 92.4 percentage of participants |
Secondary
Percentage of Participants With Viral Breakthrough
Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.
Time frame: Baseline to Week 12
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sofosbuvir+PEG+RBV | Percentage of Participants With Viral Breakthrough | 0.0 percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.
Time frame: End of treatment to post-treatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sofosbuvir+PEG+RBV | Percentage of Participants With Viral Relapse | 8.6 percentage of participants |