Hepatitis C
Conditions
Keywords
HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, Treatment-Naïve, GS-7977, Ribavirin, RBV, Peginterferon Alfa 2a, PEG, Additional relevant MeSH terms:, Hepatitis, Hepatitis A, Hepatitis, Chronic, Hepatitis C, Hepatitis C, Chronic, Liver Diseases, Digestive System Diseases, Hepatitis, Viral, Human, Virus Diseases, Enterovirus Infections, Picornaviridae Infections, RNA Virus Infections, Flaviviridae Infections, Peginterferon alfa-2a, Interferon-alpha, Antiviral Agents, Anti-Infective Agents, Therapeutic Uses, Pharmacologic Actions, Antimetabolites, Molecular Mechanisms of Pharmacological Action, Immunologic Factors, Physiological Effects of Drugs
Brief summary
This study is to evaluate the safety, tolerability, and antiviral efficacy of sofosbuvir (SOF) in combination with peginterferon alfa 2a (PEG) and ribavirin (RBV) administered for 12 weeks in participants with chronic genotype 2 or 3 hepatitis C virus (HCV) infection who have previously failed prior treatment with an interferon-based regimen.
Interventions
DRUGSOF
Sofosbuvir (SOF) 400 mg tablet administered orally once daily
DRUGPEG
Peginterferon alfa 2a (PEG) 180 μg administered once weekly by subcutaneous injection
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)
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 genotype 2 or 3 HCV infection * Cirrhosis determination * Individual is treatment-experienced * Screening laboratory values within defined thresholds * Individual has not been treated with any investigational drug or device within 30 days of the Screening visit * Use of highly effective contraception methods if female of childbearing potential or sexually active male
Exclusion criteria
* Prior exposure to a direct-acting antiviral drug targeting the HCV NS5B 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 interfere with treatment, assessment, or compliance with the study protocol * Excessive alcohol ingestion or significant drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | Posttreatment Week 12 | SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, \< 15 IU/mL) at 12 weeks after stopping study treatment. |
| Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | Up to 12 weeks | The percentage of participants discontinuing any study drug due to an adverse event was summarized. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | Posttreatment Weeks 4 and 24 | SVR4 and SVR24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. |
| Percentage of Participants Experiencing On-treatment Virologic Failure | Up to 12 weeks | On-treatment virologic failure was defined as: 1. Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 2. Viral rebound: \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 3. Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment |
| Percentage of Participants Experiencing Viral Relapse | Up to Posttreatment Week 24 | Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at a single site in the United States. The first participant was screened on 18 February 2013. The last participant observation occurred on 06 December 2013.
Pre-assignment details
56 participants were screened; 47 participants were enrolled and treated, and comprise the Safety Analysis Set and the Full Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| Genotype 2 SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 2 hepatitis C virus (HCV) infection. | 23 |
| Genotype 3 SOF 400 mg tablet once daily + PEG 180 μg subcutaneous injection once weekly + weight-based RBV (1000-1200 mg as 200 mg tablets in a divided daily dose) for 12 weeks in participants with genotype 3 HCV infection. | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Genotype 2 | Total | Genotype 3 |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 6.1 | 56 years STANDARD_DEVIATION 6.9 | 54 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 21 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 26 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV RNA Category < 6 log10 IU/mL | 4 participants | 17 participants | 13 participants |
| HCV RNA Category ≥ 6 log10 IU/mL | 19 participants | 30 participants | 11 participants |
| HCV RNA (log10 IU/mL) | 6.4 log10 IU/mL STANDARD_DEVIATION 0.66 | 6.2 log10 IU/mL STANDARD_DEVIATION 0.66 | 6.0 log10 IU/mL STANDARD_DEVIATION 0.62 |
| IL28b Status CC | 10 participants | 17 participants | 7 participants |
| IL28b Status CT | 10 participants | 25 participants | 15 participants |
| IL28b Status TT | 3 participants | 5 participants | 2 participants |
| Liver Cirrhosis No | 9 participants | 21 participants | 12 participants |
| Liver Cirrhosis Yes | 14 participants | 26 participants | 12 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 22 participants | 45 participants | 23 participants |
| Response to prior HCV treatment Nonresponse | 2 participants | 7 participants | 5 participants |
| Response to prior HCV treatment Relapse/Breakthrough | 21 participants | 40 participants | 19 participants |
| Sex: Female, Male Female | 9 Participants | 15 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 32 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 45 / 47 |
| serious Total, serious adverse events | 4 / 47 |
Outcome results
Primary
Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s)
The percentage of participants discontinuing any study drug due to an adverse event was summarized.
Time frame: Up to 12 weeks
Population: Safety Analysis Set: participants enrolled and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 2 | Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) | 8.5 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR) at 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.
Time frame: Posttreatment Week 12
Population: Full Analysis Set: participants with genotype 2 or 3 HCV infection who were enrolled and received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 2 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 95.7 percentage of participants |
| Genotype 3 | Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) | 83.3 percentage of participants |
Secondary
Percentage of Participants Experiencing On-treatment Virologic Failure
On-treatment virologic failure was defined as: 1. Viral breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 2. Viral rebound: \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value may have been posttreatment) or with a last available on-treatment measurement and no subsequent follow-up values, or 3. Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
Time frame: Up to 12 weeks
Population: Full Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 2 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
| Genotype 3 | Percentage of Participants Experiencing On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants Experiencing Viral Relapse
Viral relapse was defined as having HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at the end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.
Time frame: Up to Posttreatment Week 24
Population: Participants in the Full Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 2 | Percentage of Participants Experiencing Viral Relapse | 0 percentage of participants |
| Genotype 3 | Percentage of Participants Experiencing Viral Relapse | 8.7 percentage of participants |
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.
Time frame: Posttreatment Weeks 4 and 24
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Genotype 2 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 95.7 percentage of participants |
| Genotype 2 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 95.7 percentage of participants |
| Genotype 3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR4 | 87.5 percentage of participants |
| Genotype 3 | Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | SVR24 | 83.3 percentage of participants |