Trial Outcomes & Findings for Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir FDC and Ribavirin in Participants With Chronic Genotype 3 HCV Infection and Cirrhosis (NCT NCT02781558)
NCT ID: NCT02781558
Last Updated: 2018-11-27
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
204 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2018-11-27
Participant Flow
Participants were enrolled at study sites in Spain. The first participant was screened on 29 July 2016. The last study visit occurred on 27 October 2017.
Participant milestones
| Measure |
SOF/VEL
Sofosbuvir/velpatasvir (SOF/VEL) 400/100 mg fixed-dose combination (FDC) tablet once daily for 12 weeks
|
SOF/VEL + RBV
SOF/VEL 400/100 mg FDC tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
101
|
103
|
|
Overall Study
COMPLETED
|
98
|
101
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
SOF/VEL
Sofosbuvir/velpatasvir (SOF/VEL) 400/100 mg fixed-dose combination (FDC) tablet once daily for 12 weeks
|
SOF/VEL + RBV
SOF/VEL 400/100 mg FDC tablet once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination (FDC) and Sofosbuvir/Velpatasvir FDC and Ribavirin in Participants With Chronic Genotype 3 HCV Infection and Cirrhosis
Baseline characteristics by cohort
| Measure |
SOF/VEL
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
Total
n=204 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
51 years
STANDARD_DEVIATION 7.6 • n=7 Participants
|
51 years
STANDARD_DEVIATION 7.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
75 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
162 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
84 Participants
n=5 Participants
|
95 Participants
n=7 Participants
|
179 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
17 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
92 Participants
n=5 Participants
|
93 Participants
n=7 Participants
|
185 Participants
n=5 Participants
|
|
IL28B
CC
|
64 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
IL28B
Non-CC
|
36 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
IL28B
Missing
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
HCV RNA
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.64 • n=5 Participants
|
6.3 log10 IU/mL
STANDARD_DEVIATION 0.56 • n=7 Participants
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.60 • n=5 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
32 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
69 Participants
n=5 Participants
|
79 Participants
n=7 Participants
|
148 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: all randomized participants who took at least 1 dose of any study drug
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
SOF/VEL
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC 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 Cessation of Therapy (SVR12)
|
91.1 percentage of participants
Interval 83.8 to 95.8
|
96.1 percentage of participants
Interval 90.4 to 98.9
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Safety Analysis Set
Outcome measures
| Measure |
SOF/VEL
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC 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 (Which Included SOF/VEL and RBV) Due to Any Adverse Event
|
1.0 percentage of participants
|
1.9 percentage of participants
|
SECONDARY outcome
Timeframe: Posttreatment Week 4Population: Full Analysis Set
SVR4 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 4 weeks after stopping study treatment.
Outcome measures
| Measure |
SOF/VEL
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Attain Sustained Virologic Response at 4 Weeks After Cessation of the Study Treatment Regimen (SVR4)
|
93.1 percentage of participants
Interval 86.2 to 97.2
|
97.1 percentage of participants
Interval 91.7 to 99.4
|
SECONDARY outcome
Timeframe: Week 2Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Have HCV RNA < LLOQ at Week 2
|
51.0 percentage of participants
Interval 40.8 to 61.1
|
44.7 percentage of participants
Interval 34.9 to 54.8
|
SECONDARY outcome
Timeframe: Week 4Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Have HCV RNA < LLOQ at Week 4
|
85.0 percentage of participants
Interval 76.5 to 91.4
|
90.3 percentage of participants
Interval 82.9 to 95.2
|
SECONDARY outcome
Timeframe: Week 8Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=102 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Have HCV RNA < LLOQ at Week 8
|
99.0 percentage of participants
Interval 94.6 to 100.0
|
100.0 percentage of participants
Interval 96.4 to 100.0
|
SECONDARY outcome
Timeframe: Week 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Have HCV RNA < LLOQ at Week 12
|
99.0 percentage of participants
Interval 94.6 to 100.0
|
100.0 percentage of participants
Interval 96.4 to 100.0
|
SECONDARY outcome
Timeframe: Week 2Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=97 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=102 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
HCV RNA at Week 2
|
1.52 log10 IU/mL
Standard Deviation 0.513
|
1.47 log10 IU/mL
Standard Deviation 0.413
|
SECONDARY outcome
Timeframe: Week 4Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
HCV RNA at Week 4
|
1.22 log10 IU/mL
Standard Deviation 0.257
|
1.19 log10 IU/mL
Standard Deviation 0.152
|
SECONDARY outcome
Timeframe: Week 8Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=102 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
HCV RNA at Week 8
|
1.15 log10 IU/mL
Standard Deviation 0.040
|
1.15 log10 IU/mL
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: Week 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
HCV RNA at Week 12
|
1.15 log10 IU/mL
Standard Deviation 0.018
|
1.15 log10 IU/mL
Standard Deviation 0.000
|
SECONDARY outcome
Timeframe: Baseline; Week 2Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=97 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=102 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Change From Baseline in HCV RNA at Week 2
|
-4.67 log10 IU/mL
Standard Deviation 0.627
|
-4.80 log10 IU/mL
Standard Deviation 0.580
|
SECONDARY outcome
Timeframe: Baseline; Week 4Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Change From Baseline in HCV RNA at Week 4
|
-4.96 log10 IU/mL
Standard Deviation 0.641
|
-5.09 log10 IU/mL
Standard Deviation 0.559
|
SECONDARY outcome
Timeframe: Baseline; Week 8Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=102 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Change From Baseline in HCV RNA at Week 8
|
-5.04 log10 IU/mL
Standard Deviation 0.638
|
-5.13 log10 IU/mL
Standard Deviation 0.565
|
SECONDARY outcome
Timeframe: Baseline; Week 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL
n=100 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Change From Baseline in HCV RNA at Week 12
|
-5.04 log10 IU/mL
Standard Deviation 0.640
|
-5.13 log10 IU/mL
Standard Deviation 0.568
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 12Population: Full Analysis Set
Virologic failure was defined as * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ on 2 consecutive measurements 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) * Virologic relapse: * HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA \< LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement
Outcome measures
| Measure |
SOF/VEL
n=101 Participants
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 Participants
SOF/VEL 400/100 mg FDC tablet once daily RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Virologic Failure
|
5.9 percentage of participants
|
1.9 percentage of participants
|
Adverse Events
SOF/VEL
Serious events: 4 serious events
Other events: 24 other events
Deaths: 0 deaths
SOF/VEL + RBV
Serious events: 2 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SOF/VEL
n=101 participants at risk
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 participants at risk
SOF/VEL 400/100 mg FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Infections and infestations
Pharyngotonsillitis
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Accident at work
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer
|
0.00%
0/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.97%
1/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatocellular carcinoma
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.97%
1/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
Other adverse events
| Measure |
SOF/VEL
n=101 participants at risk
SOF/VEL 400/100 mg FDC tablet once daily for 12 weeks
|
SOF/VEL + RBV
n=103 participants at risk
SOF/VEL 400/100 mg FDC tablet once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.0%
2/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
5.8%
6/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Asthenia
|
11.9%
12/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
27.2%
28/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.9%
7/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
3.9%
4/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
7.9%
8/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
24.3%
25/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
0.99%
1/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
11.7%
12/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
2.0%
2/101 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
8.7%
9/103 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
Additional Information
Gilead Clinical Study Information Center
Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Email: [email protected]
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