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Open-Label Study of Sofusbuvir+Ribavirin With or Without Peginterferon Alfa-2a in Subjects With Chronic HCV Infection Who Participated in Prior Gilead HCV Studies

An Open-Label Study of GS-7977 + Ribavirin With or Without Peginterferon Alfa-2a in Subjects With Chronic HCV Infection Who Participated in Prior Gilead HCV Studies

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01625338
Enrollment
534
Registered
2012-06-21
Start date
2012-06-30
Completion date
2014-12-31
Last updated
2015-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C

Keywords

HCV genotype 2 (GT-2), HCV genotype 3 (GT-3), HCV, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy, GS-7977, Ribavirin, Open Label

Brief summary

This study will evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF; GS-7977) in combination with ribavirin (RBV) with or without pegylated interferon (Peg-IFN) in adults with chronic hepatitis C virus (HCV) infection who participated in a prior Gilead HCV study and have not achieved sustained virologic response (SVR).

Interventions

DRUGSOF

SOF 400 mg tablet administered orally once daily

DRUGRBV

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)

DRUGPeg-IFN

Peg-IFN 180 μg administered once weekly by subcutaneous injection

Sponsors

Gilead Sciences
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Infection with HCV * Must have participated in a prior Gilead HCV study * Use of highly effective contraception methods if female of childbearing potential or sexually active male * Eligible patients include those in the following * received placebo or Peg-IFN+RBV in a control arm * previously participated in a Gilead-sponsored HCV study and did not attain sustained virologic response 24 weeks after discontinuation of therapy (SVR24) on a regimen containing: * Sofosbuvir+RBV * Peg-IFN and/or RBV in combination with one or more Gilead investigational direct-acting agents

Exclusion criteria

* Pregnant or nursing female or male with pregnant female partner * Current or prior history of clinical hepatic decompensation * Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) * Chronic use of systemically administered immunosuppressive agents * Active drug abuse * Use of any prohibited concomitant medications

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)Posttreatment Week 12SVR12 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 EventUp to 24 weeks—

Secondary

MeasureTime frameDescription
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)Posttreatment Weeks 4 and 24SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Percentage of Participants With On-treatment Virologic FailureUp to 24 weeksOn-treatment virologic failure was defined as * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
Percentage of Participants With Viral RelapseUp to Posttreatment Week 24Viral 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

Australia, Austria, Canada, Czechia, Estonia, France, Germany, Italy, Netherlands, New Zealand, Poland, Puerto Rico, Spain, Sweden, United Kingdom, United States

Participant flow

Recruitment details

Participants were enrolled at a total of 152 study sites from their prior Gilead study in North America, Europe, Australia, and New Zealand. The first participant was screened on 22 June 2012. The last study visit occurred on 22 December 2014.

Pre-assignment details

585 participants were screened.

Participants by arm

ArmCount
SOF+RBV 12 Weeks
SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
114
SOF+RBV 24 Weeks
SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 24 weeks
200
SOF+RBV+Peg-IFN 12 Weeks
SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) + Peg-IFN 180 µg administered subcutaneously once weekly for 12 weeks in participants
219
Total533

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event101
Overall StudyEfficacy Failure273931
Overall StudyEnrolled but not Treated001
Overall StudyInvestigator Decision021
Overall StudyLost to Follow-up332
Overall StudyStudy Discontinued by Sponsor001
Overall StudySubject Withdrew Consent102

Baseline characteristics

CharacteristicTotalSOF+RBV+Peg-IFN 12 WeeksSOF+RBV 12 WeeksSOF+RBV 24 Weeks
Age, Continuous53 years
STANDARD_DEVIATION 9.1
53 years
STANDARD_DEVIATION 10
53 years
STANDARD_DEVIATION 9.6
52 years
STANDARD_DEVIATION 7.6
Cirrhosis Status
No
410 participants183 participants89 participants138 participants
Cirrhosis Status
Yes
123 participants36 participants25 participants62 participants
HCV Genotype
Genotype 1
136 participants134 participants0 participants2 participants
HCV Genotype
Genotype 2
80 participants8 participants62 participants10 participants
HCV Genotype
Genotype 3
306 participants74 participants52 participants180 participants
HCV Genotype
Genotype 4
10 participants3 participants0 participants7 participants
HCV Genotype
Indeterminate
1 participants0 participants0 participants1 participants
HCV RNA6.4 log10 IU/mL
STANDARD_DEVIATION 0.72
6.4 log10 IU/mL
STANDARD_DEVIATION 0.64
6.3 log10 IU/mL
STANDARD_DEVIATION 0.87
6.4 log10 IU/mL
STANDARD_DEVIATION 0.7
HCV RNA Category
< 800,000 IU/mL
110 participants36 participants30 participants44 participants
HCV RNA Category
≥ 800,000 IU/mL
423 participants183 participants84 participants156 participants
IL28b Status
CC
144 participants47 participants38 participants59 participants
IL28b Status
CT
291 participants127 participants61 participants103 participants
IL28b Status
Missing
10 participants5 participants2 participants3 participants
IL28b Status
TT
88 participants40 participants13 participants35 participants
Race/Ethnicity, Customized
American Indian Or Alaska Native
3 participants0 participants2 participants1 participants
Race/Ethnicity, Customized
Asian
16 participants8 participants2 participants6 participants
Race/Ethnicity, Customized
Black Or African American
26 participants20 participants4 participants2 participants
Race/Ethnicity, Customized
Hispanic or Latino
51 participants20 participants19 participants12 participants
Race/Ethnicity, Customized
Native Hawaiian Or Other Pacific Islander
2 participants0 participants0 participants2 participants
Race/Ethnicity, Customized
Not Hispanic or Latino
479 participants197 participants95 participants187 participants
Race/Ethnicity, Customized
Not Permitted
4 participants2 participants0 participants2 participants
Race/Ethnicity, Customized
Other
6 participants2 participants1 participants3 participants
Race/Ethnicity, Customized
White
476 participants187 participants105 participants184 participants
Region of Enrollment
Australia
42 participants19 participants9 participants14 participants
Region of Enrollment
Austria
4 participants1 participants1 participants2 participants
Region of Enrollment
Canada
30 participants10 participants7 participants13 participants
Region of Enrollment
Czech Republic
1 participants1 participants0 participants0 participants
Region of Enrollment
Estonia
6 participants3 participants1 participants2 participants
Region of Enrollment
France
23 participants11 participants2 participants10 participants
Region of Enrollment
Germany
32 participants18 participants2 participants12 participants
Region of Enrollment
Italy
14 participants4 participants3 participants7 participants
Region of Enrollment
Netherlands
10 participants4 participants2 participants4 participants
Region of Enrollment
New Zealand
40 participants6 participants4 participants30 participants
Region of Enrollment
Poland
9 participants8 participants0 participants1 participants
Region of Enrollment
Spain
11 participants2 participants1 participants8 participants
Region of Enrollment
Sweden
10 participants3 participants2 participants5 participants
Region of Enrollment
United Kingdom
21 participants8 participants3 participants10 participants
Region of Enrollment
United States
280 participants121 participants77 participants82 participants
Sex: Female, Male
Female
164 Participants60 Participants54 Participants50 Participants
Sex: Female, Male
Male
369 Participants159 Participants60 Participants150 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
92 / 114167 / 200194 / 219
serious
Total, serious adverse events
4 / 11411 / 2004 / 219

Outcome results

Primary

Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event

Time frame: Up to 24 weeks

Population: Safety Analysis Set: participants who were enrolled and received at least 1 dose of study drug.

ArmMeasureValue (NUMBER)
SOF+RBV 12 WeeksPercentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event0.9 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event1.0 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event3.7 percentage of participants
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, 25 IU/mL) at 12 weeks after stopping study treatment.

Time frame: Posttreatment Week 12

Population: Full Analysis Set: participants who were enrolled and received at least 1 dose of study drug.

ArmMeasureValue (NUMBER)
SOF+RBV 12 WeeksPercentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)71.9 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)77.5 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)82.6 percentage of participants
Secondary

Percentage of Participants With On-treatment Virologic Failure

On-treatment virologic failure was defined as * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

Time frame: Up to 24 weeks

Population: Full Analysis Set

ArmMeasureValue (NUMBER)
SOF+RBV 12 WeeksPercentage of Participants With On-treatment Virologic Failure0.9 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants With On-treatment Virologic Failure0.5 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants With On-treatment Virologic Failure0 percentage of participants
Secondary

Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)

SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.

Time frame: Posttreatment Weeks 4 and 24

Population: Full Analysis Set

ArmMeasureGroupValue (NUMBER)
SOF+RBV 12 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR2471.9 percentage of participants
SOF+RBV 12 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR473.7 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR481.5 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR2476.0 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR487.2 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)SVR2482.6 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: Up to Posttreatment Week 24

Population: Participants in the Full Analysis Set with available data were analyzed.

ArmMeasureValue (NUMBER)
SOF+RBV 12 WeeksPercentage of Participants With Viral Relapse25.7 percentage of participants
SOF+RBV 24 WeeksPercentage of Participants With Viral Relapse20.6 percentage of participants
SOF+RBV+Peg-IFN 12 WeeksPercentage of Participants With Viral Relapse16.4 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026