Trial Outcomes & Findings for Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir and Sofosbuvir/Velpatasvir in Adults With Chronic HCV Infection Who Have Not Previously Received Treatment With Direct-Acting Antiviral Therapy (NCT NCT02607800)
NCT ID: NCT02607800
Last Updated: 2019-03-05
Results Overview
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
943 participants
Primary outcome timeframe
Posttreatment Week 12
Results posted on
2019-03-05
Participant Flow
Participants were enrolled at study sites in North America, Europe, and, Asia Pacific. The first participant was screened on 16 November 2015. The last study visit occurred on 11 January 2017.
1116 participants were screened.
Participant milestones
| Measure |
SOF/VEL/VOX 8 Weeks
Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi®; SOF/VEL/VOX) (400/100/100 mg) fixed dose combination (FDC) tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
Sofosbuvir/Velpatasvir (Epclusa®; SOF/VEL) (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
502
|
441
|
|
Overall Study
COMPLETED
|
492
|
430
|
|
Overall Study
NOT COMPLETED
|
10
|
11
|
Reasons for withdrawal
| Measure |
SOF/VEL/VOX 8 Weeks
Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi®; SOF/VEL/VOX) (400/100/100 mg) fixed dose combination (FDC) tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
Sofosbuvir/Velpatasvir (Epclusa®; SOF/VEL) (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
7
|
10
|
|
Overall Study
Withdrew Consent
|
2
|
0
|
|
Overall Study
Randomized/Enrolled but Not Treated
|
1
|
1
|
Baseline Characteristics
Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir and Sofosbuvir/Velpatasvir in Adults With Chronic HCV Infection Who Have Not Previously Received Treatment With Direct-Acting Antiviral Therapy
Baseline characteristics by cohort
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
Total
n=941 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
52 years
STANDARD_DEVIATION 11.9 • n=7 Participants
|
52 years
STANDARD_DEVIATION 11.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
246 Participants
n=5 Participants
|
203 Participants
n=7 Participants
|
449 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
255 Participants
n=5 Participants
|
237 Participants
n=7 Participants
|
492 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
391 Participants
n=5 Participants
|
365 Participants
n=7 Participants
|
756 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
48 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
51 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
32 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
469 Participants
n=5 Participants
|
388 Participants
n=7 Participants
|
857 Participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
36 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
283 Participants
n=5 Participants
|
269 Participants
n=7 Participants
|
552 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
105 Participants
n=5 Participants
|
82 Participants
n=7 Participants
|
187 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
27 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
|
IL28b Status
CC
|
166 Participants
n=5 Participants
|
136 Participants
n=7 Participants
|
302 Participants
n=5 Participants
|
|
IL28b Status
CT
|
253 Participants
n=5 Participants
|
245 Participants
n=7 Participants
|
498 Participants
n=5 Participants
|
|
IL28b Status
TT
|
82 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
141 Participants
n=5 Participants
|
|
HCV RNA
|
6.1 log10 IU/mL
STANDARD_DEVIATION 0.75 • n=5 Participants
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.66 • n=7 Participants
|
6.2 log10 IU/mL
STANDARD_DEVIATION 0.71 • n=5 Participants
|
|
HCV RNA Category
< 800,000 IU/mL
|
155 Participants
n=5 Participants
|
138 Participants
n=7 Participants
|
293 Participants
n=5 Participants
|
|
HCV RNA Category
≥ 800,000 IU/mL
|
346 Participants
n=5 Participants
|
302 Participants
n=7 Participants
|
648 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Posttreatment Week 12Population: Full Analysis Set: all randomized/enrolled participants who took at least 1 dose of the study drug
SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
|
95.2 percentage of participants
Interval 93.0 to 96.9
|
98.2 percentage of participants
Interval 96.4 to 99.2
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: Safety Analysis Set
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Percentage of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event
|
0 percentage of participants
|
0.5 percentage of participants
|
SECONDARY outcome
Timeframe: Posttreatment Weeks 4 and 24Population: Full Analysis Set
SVR4 and SVR 24 were defined as HCV RNA \< LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR4
|
96.4 percentage of participants
Interval 94.4 to 97.9
|
98.9 percentage of participants
Interval 97.4 to 99.6
|
|
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
SVR 24
|
95.0 percentage of participants
Interval 92.7 to 96.7
|
98.0 percentage of participants
Interval 96.2 to 99.1
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 4, 8, and 12Population: Percentage of participants in Full Analysis Set with on-treatment data were analyzed.
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Percentage of Participants With HCV RNA < LLOQ On Treatment
Week 1
|
24.8 percentage of participants
Interval 21.0 to 28.8
|
22.7 percentage of participants
Interval 18.9 to 26.9
|
|
Percentage of Participants With HCV RNA < LLOQ On Treatment
Week 2
|
65.9 percentage of participants
Interval 61.5 to 70.0
|
61.3 percentage of participants
Interval 56.5 to 65.9
|
|
Percentage of Participants With HCV RNA < LLOQ On Treatment
Week 4
|
92.4 percentage of participants
Interval 89.7 to 94.6
|
92.0 percentage of participants
Interval 89.1 to 94.4
|
|
Percentage of Participants With HCV RNA < LLOQ On Treatment
Week 8
|
99.2 percentage of participants
Interval 98.0 to 99.8
|
99.8 percentage of participants
Interval 98.7 to 100.0
|
|
Percentage of Participants With HCV RNA < LLOQ On Treatment
Week 12
|
—
|
99.8 percentage of participants
Interval 98.7 to 100.0
|
SECONDARY outcome
Timeframe: Baseline; Weeks 1, 2, 4, 8, and 12Population: Participants in the Full Analysis Set with available data were analyzed.
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Change From Baseline in HCV RNA
Week 1
|
-4.23 log10 IU/mL
Standard Deviation 0.689
|
-4.24 log10 IU/mL
Standard Deviation 0.679
|
|
Change From Baseline in HCV RNA
Week 2
|
-4.75 log10 IU/mL
Standard Deviation 0.747
|
-4.77 log10 IU/mL
Standard Deviation 0.646
|
|
Change From Baseline in HCV RNA
Week 4
|
-4.95 log10 IU/mL
Standard Deviation 0.750
|
-4.99 log10 IU/mL
Standard Deviation 0.656
|
|
Change From Baseline in HCV RNA
Week 8
|
-4.99 log10 IU/mL
Standard Deviation 0.754
|
-5.03 log10 IU/mL
Standard Deviation 0.655
|
|
Change From Baseline in HCV RNA
Week 12
|
—
|
-5.03 log10 IU/mL
Standard Deviation 0.656
|
SECONDARY outcome
Timeframe: Up to Posttreatment Week 24Population: Full Analysis Set
Virologic failure was defined as: * On-treatment virologic failure: * 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) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit
Outcome measures
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 Participants
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 Participants
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Virologic Failure
|
4.2 percentage of participants
|
0.7 percentage of participants
|
Adverse Events
SOF/VEL/VOX 8 Weeks
Serious events: 15 serious events
Other events: 280 other events
Deaths: 0 deaths
SOF/VEL 12 Weeks
Serious events: 7 serious events
Other events: 213 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 participants at risk
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 participants at risk
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Cardiac disorders
Atrial fibrillation
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Chest pain
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Hepatobiliary disorders
Biliary colic
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Perineal abscess
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Pneumonia
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Infections and infestations
Pyelonephritis
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Multiple fractures
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Alcohol withdrawal syndrome
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Depression
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.23%
1/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Vascular disorders
Peripheral artery occlusion
|
0.20%
1/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
0.00%
0/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
Other adverse events
| Measure |
SOF/VEL/VOX 8 Weeks
n=501 participants at risk
SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 8 weeks
|
SOF/VEL 12 Weeks
n=440 participants at risk
SOF/VEL (400/100 mg) FDC tablet orally once daily with or without food for 12 weeks
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
17.6%
88/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
7.3%
32/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
16.0%
80/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
9.1%
40/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Asthenia
|
6.4%
32/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
6.1%
27/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
General disorders
Fatigue
|
21.2%
106/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
20.7%
91/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.8%
19/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
5.5%
24/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
26.7%
134/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
22.5%
99/440 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
|
Psychiatric disorders
Insomnia
|
5.2%
26/501 • Up to 12 weeks plus 30 days
Safety Analysis Set
|
4.8%
21/440 • Up to 12 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