Safety and Efficacy of Sofosbuvir Plus Velpatasvir With or Without Ribavirin in Treatment-experienced Subjects With Chronic HCV Infection
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01909804
Collaborator
(none)
323
49
12
14
6.6
0.5
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) + velpatasvir (VEL; GS-5816) with or without ribavirin (RBV) in treatment-naive adults with chronic genotype (GT) 1 or 3 hepatitis C virus (HCV) infection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
323 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Randomized, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir + GS-5816 for 12 Weeks in Treatment-Experienced Subjects With Chronic HCV Infection
Study Start Date
:
Jun 1, 2013
Actual Primary Completion Date
:
May 1, 2014
Actual Study Completion Date
:
Aug 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SOF+VEL 25 mg (GT3) without cirrhosis Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 25 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 25mg+RBV (GT3) without cirrhosis Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 25 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
| Experimental: SOF+VEL 100 mg (GT3) without cirrhosis Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 100 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 100 mg+RBV (GT3) without cirrhosis Participants with genotype 3 HCV infection without cirrhosis will receive SOF+VEL 100 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
| Experimental: SOF+VEL 25 mg (GT3) with cirrhosis Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 25 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 25 mg+RBV (GT3) with cirrhosis Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 25 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
| Experimental: SOF+VEL 100 mg (GT3) with cirrhosis Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 100 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 100 mg+RBV (GT3) with cirrhosis Participants with genotype 3 HCV infection with cirrhosis will receive SOF+VEL 100 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
| Experimental: SOF+VEL 25 mg (GT1) Participants with genotype 1 HCV infection will receive SOF+VEL 25 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 25 mg+RBV (GT1) Participants with genotype 1 HCV infection will receive SOF+VEL 25 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
| Experimental: SOF+VEL 100 mg (GT1) Participants with genotype 1 HCV infection will receive SOF+VEL 100 mg for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
|
| Experimental: SOF+VEL 100 mg+RBV (GT1) Participants with genotype 1 HCV infection will receive SOF+VEL 100 mg plus RBV for 12 weeks. |
Drug: SOF
400 mg tablet administered orally once daily
Other Names:
Drug: VEL
Tablet administered orally once daily
Other Names:
Drug: RBV
200 mg 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)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Sustained Virologic Response (SVR) 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.
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [Up to 12 weeks]
Secondary Outcome Measures
- Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]
SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
- Percentage of Participants With Virologic Failure [Up to Posttreatment Week 24]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Body mass index (BMI) ≥ 18 kg/m^2
-
HCV RNA ≥ 10000 IU/mL at screening
-
Prior treatment failure to a regimen including interferon with or without RBV
-
HCV genotype 1 or 3
-
Chronic HCV infection
-
Cirrhosis determination
-
Use of highly effective contraception methods if female of childbearing potential or sexually active male
Exclusion Criteria:
-
Current or prior history of clinically significant illness other than HCV
-
Screening ECG with clinically significant abnormalities
-
Prior exposure to HCV specific direct acting antiviral agent
-
Pregnant or nursing female or male with pregnant female partner
-
Chronic liver disease of non-HCV etiology
-
Hepatitis B
-
Active drug abuse
-
Use of any prohibited concomitant medications
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Long Beach | California | United States | ||
| 2 | Los Angeles | California | United States | ||
| 3 | Pasadena | California | United States | ||
| 4 | San Diego | California | United States | ||
| 5 | Denver | Colorado | United States | ||
| 6 | Gainesville | Florida | United States | ||
| 7 | Jacksonville | Florida | United States | ||
| 8 | Miami | Florida | United States | ||
| 9 | Orlando | Florida | United States | ||
| 10 | Tampa | Florida | United States | ||
| 11 | Wellington | Florida | United States | ||
| 12 | Atlanta | Georgia | United States | ||
| 13 | Marietta | Georgia | United States | ||
| 14 | Chicago | Illinois | United States | ||
| 15 | Indianapolis | Indiana | United States | ||
| 16 | Baltimore | Maryland | United States | ||
| 17 | Boston | Massachusetts | United States | ||
| 18 | Detroit | Michigan | United States | ||
| 19 | Hillsborough | New Jersey | United States | ||
| 20 | Santa Fe | New Mexico | United States | ||
| 21 | Great Neck | New York | United States | ||
| 22 | New York | New York | United States | ||
| 23 | Asheville | North Carolina | United States | ||
| 24 | Durham | North Carolina | United States | ||
| 25 | Fayetteville | North Carolina | United States | ||
| 26 | Winston-Salem | North Carolina | United States | ||
| 27 | Portland | Oregon | United States | ||
| 28 | Philadelphia | Pennsylvania | United States | ||
| 29 | Pittsburgh | Pennsylvania | United States | ||
| 30 | Providence | Rhode Island | United States | ||
| 31 | Germantown | Tennessee | United States | ||
| 32 | Nashville | Tennessee | United States | ||
| 33 | Arlington | Texas | United States | ||
| 34 | Dallas | Texas | United States | ||
| 35 | San Antonio | Texas | United States | ||
| 36 | Annandale | Virginia | United States | ||
| 37 | Fairfax | Virginia | United States | ||
| 38 | Newport News | Virginia | United States | ||
| 39 | Norfolk | Virginia | United States | ||
| 40 | Seattle | Washington | United States | ||
| 41 | Camperdown | New South Wales | Australia | ||
| 42 | Darlinghurst | New South Wales | Australia | ||
| 43 | Clayton | Victoria | Australia | ||
| 44 | Melbourne | Victoria | Australia | ||
| 45 | Fremantle | Western Australia | Australia | ||
| 46 | Perth | Western Australia | Australia | ||
| 47 | Auckland | New Zealand | |||
| 48 | Christchurch | New Zealand | |||
| 49 | San Juan | Puerto Rico |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: John McNally, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01909804
Other Study ID Numbers:
- GS-US-342-0109
First Posted:
Jul 29, 2013
Last Update Posted:
Nov 15, 2018
Last Verified:
Jul 1, 2016
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Gilead Sciences
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at study sites in Australia, New Zealand, and the United States. The first participant was screened on 17 June 2013. The last study visit occurred on 22 August 2014. |
|---|---|
| Pre-assignment Detail | 416 participants were screened. |
| Arm/Group Title | SOF+VEL 25 mg (GT3 Non-Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 100 mg (GT3 Non-Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 25 mg (GT3 Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Cirrhotic) | SOF+VEL 100 mg (GT3 Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Cirrhotic) | SOF+VEL 25 mg (GT1) | SOF+VEL 25 mg + RBV (GT1) | SOF+VEL 100 mg (GT1) | SOF+VEL 100 mg + RBV (GT1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Sofosbuvir (SOF) 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype (GT) 3 non-cirrhotic) | SOF 400 mg tablet + velpatasvir (VEL) 25 mg tablet administered orally once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) |
| Period Title: Overall Study | ||||||||||||
| STARTED | 26 | 28 | 27 | 26 | 26 | 25 | 27 | 26 | 27 | 29 | 27 | 29 |
| COMPLETED | 22 | 27 | 27 | 26 | 18 | 21 | 25 | 25 | 27 | 28 | 26 | 26 |
| NOT COMPLETED | 4 | 1 | 0 | 0 | 8 | 4 | 2 | 1 | 0 | 1 | 1 | 3 |
Baseline Characteristics
| Arm/Group Title | SOF+VEL 25 mg (GT3 Non-Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 100 mg (GT3 Non-Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 25 mg (GT3 Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Cirrhotic) | SOF+VEL 100 mg (GT3 Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Cirrhotic) | SOF+VEL 25 mg (GT1) | SOF+VEL 25 mg + RBV (GT1) | SOF+VEL 100 mg (GT1) | SOF+VEL 100 mg + RBV (GT1) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype (GT) 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | Total of all reporting groups |
| Overall Participants | 26 | 28 | 27 | 26 | 26 | 25 | 26 | 26 | 27 | 29 | 27 | 28 | 321 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [years] |
54
(11.8)
|
51
(10.4)
|
55
(6.9)
|
56
(6.4)
|
57
(7.0)
|
56
(5.6)
|
56
(5.7)
|
54
(4.7)
|
55
(8.1)
|
57
(5.8)
|
57
(6.4)
|
56
(6.0)
|
55
(7.4)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||
| Female |
8
30.8%
|
6
21.4%
|
9
33.3%
|
9
34.6%
|
5
19.2%
|
10
40%
|
6
23.1%
|
6
23.1%
|
12
44.4%
|
7
24.1%
|
12
44.4%
|
10
35.7%
|
100
31.2%
|
| Male |
18
69.2%
|
22
78.6%
|
18
66.7%
|
17
65.4%
|
21
80.8%
|
15
60%
|
20
76.9%
|
20
76.9%
|
15
55.6%
|
22
75.9%
|
15
55.6%
|
18
64.3%
|
221
68.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||||||
| Hispanic or Latino |
1
3.8%
|
2
7.1%
|
1
3.7%
|
2
7.7%
|
1
3.8%
|
1
4%
|
2
7.7%
|
0
0%
|
2
7.4%
|
1
3.4%
|
4
14.8%
|
3
10.7%
|
20
6.2%
|
| Not Hispanic or Latino |
25
96.2%
|
26
92.9%
|
26
96.3%
|
24
92.3%
|
25
96.2%
|
24
96%
|
24
92.3%
|
26
100%
|
25
92.6%
|
28
96.6%
|
23
85.2%
|
25
89.3%
|
301
93.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
3.7%
|
1
3.8%
|
0
0%
|
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3.6%
|
4
1.2%
|
| Asian |
1
3.8%
|
1
3.6%
|
1
3.7%
|
0
0%
|
1
3.8%
|
2
8%
|
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
2
7.1%
|
9
2.8%
|
| Black or African American |
0
0%
|
1
3.6%
|
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7
25.9%
|
2
6.9%
|
4
14.8%
|
4
14.3%
|
19
5.9%
|
| Native Hawaiian or Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
| White |
25
96.2%
|
26
92.9%
|
25
92.6%
|
24
92.3%
|
25
96.2%
|
23
92%
|
25
96.2%
|
24
92.3%
|
20
74.1%
|
27
93.1%
|
23
85.2%
|
21
75%
|
288
89.7%
|
| HCV Genotype (participants) [Number] | |||||||||||||
| Genotype 1a |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
19
70.4%
|
22
75.9%
|
21
77.8%
|
22
78.6%
|
84
26.2%
|
| Genotype 1b |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7
25.9%
|
7
24.1%
|
6
22.2%
|
6
21.4%
|
26
8.1%
|
| Genotype 1 (no confirmed subtype) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
0
0%
|
0
0%
|
0
0%
|
1
0.3%
|
| Genotype 3 |
26
100%
|
28
100%
|
27
100%
|
26
100%
|
26
100%
|
25
100%
|
26
100%
|
26
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
210
65.4%
|
| IL28b Status (participants) [Number] | |||||||||||||
| CC |
8
30.8%
|
10
35.7%
|
8
29.6%
|
11
42.3%
|
12
46.2%
|
5
20%
|
12
46.2%
|
13
50%
|
0
0%
|
1
3.4%
|
2
7.4%
|
3
10.7%
|
85
26.5%
|
| CT |
16
61.5%
|
14
50%
|
13
48.1%
|
12
46.2%
|
11
42.3%
|
14
56%
|
11
42.3%
|
10
38.5%
|
19
70.4%
|
21
72.4%
|
17
63%
|
19
67.9%
|
177
55.1%
|
| TT |
2
7.7%
|
4
14.3%
|
6
22.2%
|
3
11.5%
|
3
11.5%
|
6
24%
|
3
11.5%
|
3
11.5%
|
8
29.6%
|
7
24.1%
|
8
29.6%
|
6
21.4%
|
59
18.4%
|
| Cirrhosis Status (participants) [Number] | |||||||||||||
| Absent |
25
96.2%
|
27
96.4%
|
27
100%
|
24
92.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
17
63%
|
19
65.5%
|
18
66.7%
|
18
64.3%
|
175
54.5%
|
| Present |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
26
100%
|
25
100%
|
26
100%
|
26
100%
|
8
29.6%
|
10
34.5%
|
7
25.9%
|
10
35.7%
|
138
43%
|
| Missing |
1
3.8%
|
1
3.6%
|
0
0%
|
2
7.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
7.4%
|
0
0%
|
2
7.4%
|
0
0%
|
8
2.5%
|
| HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [log10 IU/mL] |
6.7
(0.76)
|
6.6
(0.70)
|
6.6
(0.59)
|
6.7
(0.53)
|
6.6
(0.46)
|
6.2
(0.68)
|
6.4
(0.76)
|
6.7
(0.51)
|
6.5
(0.59)
|
6.8
(0.37)
|
6.4
(0.53)
|
6.5
(0.43)
|
6.6
(0.60)
|
| HCV RNA Category (participants) [Number] | |||||||||||||
| < 800,000 IU/mL |
5
19.2%
|
6
21.4%
|
2
7.4%
|
2
7.7%
|
3
11.5%
|
7
28%
|
7
26.9%
|
2
7.7%
|
6
22.2%
|
0
0%
|
3
11.1%
|
3
10.7%
|
46
14.3%
|
| ≥ 800,000 IU/mL |
21
80.8%
|
22
78.6%
|
25
92.6%
|
24
92.3%
|
23
88.5%
|
18
72%
|
19
73.1%
|
24
92.3%
|
21
77.8%
|
29
100%
|
24
88.9%
|
25
89.3%
|
275
85.7%
|
| Prior HCV Treatment (participants) [Number] | |||||||||||||
| Non-responder |
7
26.9%
|
10
35.7%
|
7
25.9%
|
5
19.2%
|
6
23.1%
|
9
36%
|
10
38.5%
|
3
11.5%
|
6
22.2%
|
13
44.8%
|
7
25.9%
|
8
28.6%
|
91
28.3%
|
| Relapse / Breakthrough |
19
73.1%
|
18
64.3%
|
20
74.1%
|
21
80.8%
|
20
76.9%
|
16
64%
|
16
61.5%
|
23
88.5%
|
21
77.8%
|
16
55.2%
|
20
74.1%
|
20
71.4%
|
230
71.7%
|
Outcome Measures
| Title | Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: participants randomized into the study and received at least 1 dose of study drug. |
| Arm/Group Title | SOF+VEL 25 mg (GT3 Non-Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 100 mg (GT3 Non-Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 25 mg (GT3 Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Cirrhotic) | SOF+VEL 100 mg (GT3 Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Cirrhotic) | SOF+VEL 25 mg (GT1) | SOF+VEL 25 mg + RBV (GT1) | SOF+VEL 100 mg (GT1) | SOF+VEL 100 mg + RBV (GT1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype (GT) 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) |
| Measure Participants | 26 | 28 | 27 | 26 | 26 | 25 | 26 | 26 | 27 | 29 | 27 | 28 |
| Number (95% Confidence Interval) [percentage of participants] |
84.6
325.4%
|
96.4
344.3%
|
100.0
370.4%
|
100.0
384.6%
|
57.7
221.9%
|
84.0
336%
|
88.5
340.4%
|
96.2
370%
|
100.0
370.4%
|
96.6
333.1%
|
100.0
370.4%
|
96.4
344.3%
|
| Title | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |
|---|---|
| Description | |
| Time Frame | Up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | SOF+VEL 25 mg | SOF+VEL 25 mg + RBV | SOF+VEL 100 mg | SOF+VEL 100 mg + RBV |
|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotypes 1 and 3) |
| Measure Participants | 79 | 82 | 80 | 80 |
| Number [percentage of participants] |
0
0%
|
1.2
4.3%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | SOF+VEL 25 mg (GT3 Non-Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 100 mg (GT3 Non-Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 25 mg (GT3 Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Cirrhotic) | SOF+VEL 100 mg (GT3 Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Cirrhotic) | SOF+VEL 25 mg (GT1) | SOF+VEL 25 mg + RBV (GT1) | SOF+VEL 100 mg (GT1) | SOF+VEL 100 mg + RBV (GT1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype (GT) 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) |
| Measure Participants | 26 | 28 | 27 | 26 | 26 | 25 | 26 | 26 | 27 | 29 | 27 | 28 |
| SVR4 |
88.5
340.4%
|
96.4
344.3%
|
100.0
370.4%
|
100.0
384.6%
|
61.5
236.5%
|
84.0
336%
|
88.5
340.4%
|
96.2
370%
|
100.0
370.4%
|
96.6
333.1%
|
100.0
370.4%
|
96.4
344.3%
|
| SVR24 |
84.6
325.4%
|
96.4
344.3%
|
100.0
370.4%
|
100.0
384.6%
|
57.7
221.9%
|
84.0
336%
|
92.3
355%
|
96.2
370%
|
100.0
370.4%
|
96.6
333.1%
|
100.0
370.4%
|
96.4
344.3%
|
| Title | Percentage of Participants With Virologic Failure |
|---|---|
| Description | 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. |
| Time Frame | Up to Posttreatment Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | SOF+VEL 25 mg (GT3 Non-Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 100 mg (GT3 Non-Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Non-Cirrhotic) | SOF+VEL 25 mg (GT3 Cirrhotic) | SOF+VEL 25 mg + RBV (GT3 Cirrhotic) | SOF+VEL 100 mg (GT3 Cirrhotic) | SOF+VEL 100 mg + RBV (GT3 Cirrhotic) | SOF+VEL 25 mg (GT1) | SOF+VEL 25 mg + RBV (GT1) | SOF+VEL 100 mg (GT1) | SOF+VEL 100 mg + RBV (GT1) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype (GT) 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 non-cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 3 cirrhotic) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotype 1) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotype 1) |
| Measure Participants | 26 | 28 | 27 | 26 | 26 | 25 | 26 | 26 | 27 | 29 | 27 | 28 |
| Number [percentage of participants] |
15.4
59.2%
|
3.6
12.9%
|
0
0%
|
0
0%
|
42.3
162.7%
|
12.0
48%
|
11.5
44.2%
|
3.8
14.6%
|
0
0%
|
3.4
11.7%
|
0
0%
|
3.6
12.9%
|
Adverse Events
| Time Frame | Up to 12 weeks plus 30 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set | |||||||
| Arm/Group Title | SOF+VEL 25 mg | SOF+VEL 25 mg + RBV | SOF+VEL 100 mg | SOF+VEL 100 mg + RBV | ||||
| Arm/Group Description | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 25 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily for 12 weeks (genotypes 1 and 3) | SOF 400 mg tablet + VEL 100 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks (genotypes 1 and 3) | ||||
All Cause Mortality |
||||||||
| SOF+VEL 25 mg | SOF+VEL 25 mg + RBV | SOF+VEL 100 mg | SOF+VEL 100 mg + RBV | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| SOF+VEL 25 mg | SOF+VEL 25 mg + RBV | SOF+VEL 100 mg | SOF+VEL 100 mg + RBV | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/79 (1.3%) | 0/82 (0%) | 4/80 (5%) | 3/80 (3.8%) | ||||
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/79 (0%) | 0/82 (0%) | 0/80 (0%) | 1/80 (1.3%) | ||||
| Atrial fibrillation | 0/79 (0%) | 0/82 (0%) | 1/80 (1.3%) | 0/80 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/79 (0%) | 0/82 (0%) | 0/80 (0%) | 1/80 (1.3%) | ||||
| General disorders | ||||||||
| Drug withdrawal syndrome | 0/79 (0%) | 0/82 (0%) | 0/80 (0%) | 1/80 (1.3%) | ||||
| Thrombosis in device | 0/79 (0%) | 0/82 (0%) | 1/80 (1.3%) | 0/80 (0%) | ||||
| Infections and infestations | ||||||||
| Viral infection | 1/79 (1.3%) | 0/82 (0%) | 0/80 (0%) | 0/80 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Hypersensitivity vasculitis | 0/79 (0%) | 0/82 (0%) | 1/80 (1.3%) | 0/80 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/79 (0%) | 0/82 (0%) | 1/80 (1.3%) | 0/80 (0%) | ||||
| May-Thurner syndrome | 0/79 (0%) | 0/82 (0%) | 1/80 (1.3%) | 0/80 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| SOF+VEL 25 mg | SOF+VEL 25 mg + RBV | SOF+VEL 100 mg | SOF+VEL 100 mg + RBV | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 54/79 (68.4%) | 61/82 (74.4%) | 54/80 (67.5%) | 62/80 (77.5%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/79 (0%) | 4/82 (4.9%) | 0/80 (0%) | 5/80 (6.3%) | ||||
| Gastrointestinal disorders | ||||||||
| Constipation | 4/79 (5.1%) | 3/82 (3.7%) | 4/80 (5%) | 6/80 (7.5%) | ||||
| Diarrhoea | 9/79 (11.4%) | 4/82 (4.9%) | 9/80 (11.3%) | 4/80 (5%) | ||||
| Dyspepsia | 2/79 (2.5%) | 3/82 (3.7%) | 4/80 (5%) | 6/80 (7.5%) | ||||
| Gastrooesophageal reflux disease | 4/79 (5.1%) | 2/82 (2.4%) | 1/80 (1.3%) | 4/80 (5%) | ||||
| Nausea | 12/79 (15.2%) | 18/82 (22%) | 7/80 (8.8%) | 18/80 (22.5%) | ||||
| Vomiting | 1/79 (1.3%) | 4/82 (4.9%) | 1/80 (1.3%) | 4/80 (5%) | ||||
| General disorders | ||||||||
| Fatigue | 16/79 (20.3%) | 27/82 (32.9%) | 19/80 (23.8%) | 27/80 (33.8%) | ||||
| Influenza like illness | 0/79 (0%) | 1/82 (1.2%) | 4/80 (5%) | 1/80 (1.3%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 1/79 (1.3%) | 2/82 (2.4%) | 2/80 (2.5%) | 4/80 (5%) | ||||
| Upper respiratory tract infection | 6/79 (7.6%) | 7/82 (8.5%) | 5/80 (6.3%) | 3/80 (3.8%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Laceration | 0/79 (0%) | 2/82 (2.4%) | 1/80 (1.3%) | 4/80 (5%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 4/79 (5.1%) | 3/82 (3.7%) | 1/80 (1.3%) | 2/80 (2.5%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 3/79 (3.8%) | 4/82 (4.9%) | 7/80 (8.8%) | 3/80 (3.8%) | ||||
| Back pain | 3/79 (3.8%) | 6/82 (7.3%) | 3/80 (3.8%) | 2/80 (2.5%) | ||||
| Muscle spasms | 2/79 (2.5%) | 1/82 (1.2%) | 1/80 (1.3%) | 4/80 (5%) | ||||
| Myalgia | 1/79 (1.3%) | 4/82 (4.9%) | 6/80 (7.5%) | 4/80 (5%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 7/79 (8.9%) | 8/82 (9.8%) | 1/80 (1.3%) | 4/80 (5%) | ||||
| Headache | 23/79 (29.1%) | 28/82 (34.1%) | 18/80 (22.5%) | 24/80 (30%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 12/79 (15.2%) | 11/82 (13.4%) | 6/80 (7.5%) | 16/80 (20%) | ||||
| Irritability | 6/79 (7.6%) | 6/82 (7.3%) | 3/80 (3.8%) | 12/80 (15%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 5/79 (6.3%) | 5/82 (6.1%) | 4/80 (5%) | 7/80 (8.8%) | ||||
| Dyspnoea | 0/79 (0%) | 6/82 (7.3%) | 1/80 (1.3%) | 5/80 (6.3%) | ||||
| Dyspnoea exertional | 0/79 (0%) | 3/82 (3.7%) | 0/80 (0%) | 5/80 (6.3%) | ||||
| Epistaxis | 4/79 (5.1%) | 1/82 (1.2%) | 0/80 (0%) | 0/80 (0%) | ||||
| Oropharyngeal pain | 4/79 (5.1%) | 5/82 (6.1%) | 1/80 (1.3%) | 1/80 (1.3%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dry skin | 1/79 (1.3%) | 6/82 (7.3%) | 1/80 (1.3%) | 1/80 (1.3%) | ||||
| Pruritus | 2/79 (2.5%) | 9/82 (11%) | 2/80 (2.5%) | 12/80 (15%) | ||||
| Rash | 4/79 (5.1%) | 5/82 (6.1%) | 2/80 (2.5%) | 9/80 (11.3%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Results Point of Contact
| Name/Title | Clinical Trial Disclosures |
|---|---|
| Organization | Gilead Sciences |
| Phone | |
| ClinicalTrialDisclosures@gilead.com |
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01909804
Other Study ID Numbers:
- GS-US-342-0109
First Posted:
Jul 29, 2013
Last Update Posted:
Nov 15, 2018
Last Verified:
Jul 1, 2016