Trial Outcomes & Findings for Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis (NCT NCT02128542)
NCT ID: NCT02128542
Last Updated: 2016-08-03
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
66 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2016-08-03
Participant Flow
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.
113 participants were screened.
Participant milestones
| Measure |
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.
|
SOF+RBV 12 Weeks (TE)
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.
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
19
|
|
Overall Study
COMPLETED
|
43
|
19
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
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.
|
SOF+RBV 12 Weeks (TE)
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.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
|
Overall Study
Withdrew Consent
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Sofosbuvir+Ribavirin in Genotype 2 HCV-infected U.S. Veterans With Cirrhosis
Baseline characteristics by cohort
| Measure |
SOF+RBV 12 Weeks (TN)
n=47 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
SOF+RBV 12 Weeks (TE)
n=19 Participants
Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64 Years
STANDARD_DEVIATION 6.0 • n=93 Participants
|
62 Years
STANDARD_DEVIATION 5.4 • n=4 Participants
|
63 Years
STANDARD_DEVIATION 5.8 • n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=93 Participants
|
19 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
8 participants
n=93 Participants
|
2 participants
n=4 Participants
|
10 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
37 participants
n=93 Participants
|
17 participants
n=4 Participants
|
54 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Hawaiian or Pacific Islander
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=93 Participants
|
0 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
United States
|
47 participants
n=93 Participants
|
19 participants
n=4 Participants
|
66 participants
n=27 Participants
|
|
IL28b Status
CC
|
25 participants
n=93 Participants
|
8 participants
n=4 Participants
|
33 participants
n=27 Participants
|
|
IL28b Status
CT
|
19 participants
n=93 Participants
|
10 participants
n=4 Participants
|
29 participants
n=27 Participants
|
|
IL28b Status
TT
|
3 participants
n=93 Participants
|
1 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
HCV RNA
|
5.9 log10 IU/mL
STANDARD_DEVIATION 0.89 • n=93 Participants
|
6.6 log10 IU/mL
STANDARD_DEVIATION 0.48 • n=4 Participants
|
6.1 log10 IU/mL
STANDARD_DEVIATION 0.87 • n=27 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
21 participants
n=93 Participants
|
2 participants
n=4 Participants
|
23 participants
n=27 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
26 participants
n=93 Participants
|
17 participants
n=4 Participants
|
43 participants
n=27 Participants
|
|
HCV Genotype
Genotype 2
|
2 participants
n=93 Participants
|
2 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
HCV Genotype
Genotype 2b
|
37 participants
n=93 Participants
|
17 participants
n=4 Participants
|
54 participants
n=27 Participants
|
|
HCV Genotype
Genotype 2a/2c
|
8 participants
n=93 Participants
|
0 participants
n=4 Participants
|
8 participants
n=27 Participants
|
|
Cirrhosis Status
No
|
0 participants
n=93 Participants
|
0 participants
n=4 Participants
|
0 participants
n=27 Participants
|
|
Cirrhosis Status
Yes
|
47 participants
n=93 Participants
|
19 participants
n=4 Participants
|
66 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=47 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
SOF+RBV 12 Weeks (TE)
n=19 Participants
Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy
|
76.6 Percentage of participants
Interval 62.0 to 87.7
|
84.2 Percentage of participants
Interval 60.4 to 96.6
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set: participants who received at least 1 dose of study drug
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=66 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
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.
|
|---|---|---|
|
Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
|
4.5 Percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Posttreatment Week 4Population: Full Analysis Set
SVR4 was defined as HCV RNA \< LLOQ at 4 weeks following the last dose of study drug.
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=47 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
SOF+RBV 12 Weeks (TE)
n=19 Participants
Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response at 4 Weeks After Discontinuation of Therapy (SVR4)
|
78.7 percentage of participants
Interval 64.3 to 89.3
|
89.5 percentage of participants
Interval 66.9 to 98.7
|
SECONDARY outcome
Timeframe: Up to Posttreatment Weak 12Population: Full Analysis Set
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
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=47 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
SOF+RBV 12 Weeks (TE)
n=19 Participants
Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|---|
|
Percentage of Participants Experiencing Viral Breakthrough
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 12Population: Participants in the Full Analysis Set with available data were analyzed .
Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA \< LLOQ at end of treatment.
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=46 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
SOF+RBV 12 Weeks (TE)
n=19 Participants
Treatment-experienced participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|---|
|
Percentage of Participants Experiencing Viral Relapse
|
17.4 Percentage of participants
|
15.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Pretreatment and Posttreatment Week 12Population: Participants who relapsed and qualified for sequencing analysis were analyzed.
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.
Outcome measures
| Measure |
SOF+RBV 12 Weeks (TN)
n=10 Participants
Treatment-naive participants received SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
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.
|
|---|---|---|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
|
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
|
—
|
Adverse Events
SOF+RBV 12 Weeks (All Participants)
Serious events: 8 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SOF+RBV 12 Weeks (All Participants)
n=66 participants at risk
SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Cardiac disorders
Cardiac failure congestive
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Chest pain
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Bacteraemia
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Endocarditis staphylococcal
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Sepsis
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Drug withdrawal convulsions
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
1.5%
1/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
Other adverse events
| Measure |
SOF+RBV 12 Weeks (All Participants)
n=66 participants at risk
SOF 400 mg tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
24.2%
16/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Dyspepsia
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
18.2%
12/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Vomiting
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Fatigue
|
33.3%
22/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Dizziness
|
9.1%
6/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
16.7%
11/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Depression
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
6.1%
4/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.6%
5/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.6%
5/66 • Up to12 weeks plus 30 days
Safety Analysis Set
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER