ASTRAL-4: Sofosbuvir/Velpatasvir Fixed-Dose Combination in Adults With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT02201901
Collaborator
(none)
268
50
3
16
5.4
0.3
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of sofosbuvir (SOF)/velpatasvir (VEL) fixed dose combination (FDC) with and without ribavirin (RBV) for 12 weeks and SOF/VEL FDC for 24 weeks in adults with chronic hepatitis C virus (HCV) infection and Child-Pugh-Turcotte (CPT) class B cirrhosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
268 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/GS-5816 Fixed-Dose Combination in Subjects With Chronic HCV Infection and Child-Pugh Class B Cirrhosis
Study Start Date
:
Jul 1, 2014
Actual Primary Completion Date
:
Aug 1, 2015
Actual Study Completion Date
:
Nov 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SOF/VEL 12 weeks Participants will receive SOF/VEL FDC for 12 weeks. |
Drug: SOF/VEL
400/100 mg tablets administered orally once daily
Other Names:
|
| Experimental: SOF/VEL+RBV 12 weeks Participants will receive SOF/VEL FDC plus RBV for 12 weeks. |
Drug: SOF/VEL
400/100 mg tablets administered orally once daily
Other Names:
Drug: RBV
Ribavirin (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)
|
| Experimental: SOF/VEL 24 weeks Participants will receive SOF/VEL FDC for 24 weeks. |
Drug: SOF/VEL
400/100 mg tablets administered orally once daily
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) 12 weeks following the last dose of study drug.
- Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [Up to 24 weeks plus 30 days]
Secondary Outcome Measures
- Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]
SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
- Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 [Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24]
- Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 [Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24]
- Percentage of Participants With Virologic Failure [Up to Posttreatment Week 24]
Virologic failure was defined as On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) Relapse 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
- Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score [Baseline to Posttreatment Week 24]
Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.
- Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score [Baseline to Posttreatment Week 24]
CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Willing and able to provide written informed consent
-
HCV RNA > 10^4 IU/mL at screening
-
Chronic HCV infection (≥ 6 months)
-
Confirmed CPT class B (7-9) at screening
Exclusion Criteria:
-
Current or prior history of solid organ transplantation, significant pulmonary disease, significant cardiac disease, or porphyria
-
Inability to exclude hepatocellular carcinoma (HCC) by imaging within 6 months of baseline/Day 1
-
Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
-
Screening ECG with clinically significant abnormalities
-
Prior exposure to SOF or any other nucleotide analogue HCV nonstructural protein 5B (NS5B) inhibitor or any HCV NS5A inhibitor
-
Laboratory results outside of acceptable ranges at screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | ||
| 2 | La Jolla | California | United States | ||
| 3 | Los Angeles | California | United States | 90048 | |
| 4 | Los Angeles | California | United States | ||
| 5 | Pasadena | California | United States | ||
| 6 | San Francisco | California | United States | ||
| 7 | Aurora | Colorado | United States | ||
| 8 | Washington | District of Columbia | United States | ||
| 9 | Gainesville | Florida | United States | ||
| 10 | Jacksonville | Florida | United States | 32256 | |
| 11 | Miami | Florida | United States | ||
| 12 | Tampa | Florida | United States | ||
| 13 | Marietta | Georgia | United States | ||
| 14 | Chicago | Illinois | United States | ||
| 15 | Indianapolis | Indiana | United States | 46202 | |
| 16 | Indianapolis | Indiana | United States | 46237 | |
| 17 | Kansas City | Kansas | United States | ||
| 18 | Monroe | Louisiana | United States | 71280 | |
| 19 | New Orleans | Louisiana | United States | ||
| 20 | Baltimore | Maryland | United States | ||
| 21 | Boston | Massachusetts | United States | ||
| 22 | Ann Arbor | Michigan | United States | ||
| 23 | Detroit | Michigan | United States | ||
| 24 | Rochester | Minnesota | United States | ||
| 25 | Jackson | Mississippi | United States | ||
| 26 | Saint Louis | Missouri | United States | ||
| 27 | Santa Fe | New Mexico | United States | 87505 | |
| 28 | New York | New York | United States | 10016 | |
| 29 | New York | New York | United States | 10029 | |
| 30 | New York | New York | United States | 10032 | |
| 31 | Chapel Hill | North Carolina | United States | ||
| 32 | Charlotte | North Carolina | United States | 28204 | |
| 33 | Durham | North Carolina | United States | ||
| 34 | Cleveland | Ohio | United States | 44195 | |
| 35 | Cleveland | Ohio | United States | ||
| 36 | Philadelphia | Pennsylvania | United States | 19104 | |
| 37 | Philadelphia | Pennsylvania | United States | 19107 | |
| 38 | Pittsburgh | Pennsylvania | United States | ||
| 39 | Providence | Rhode Island | United States | 02905 | |
| 40 | Germantown | Tennessee | United States | 38138 | |
| 41 | Nashville | Tennessee | United States | 37211 | |
| 42 | Arlington | Texas | United States | 76012 | |
| 43 | Dallas | Texas | United States | ||
| 44 | San Antonio | Texas | United States | ||
| 45 | Murray | Utah | United States | ||
| 46 | Fairfax | Virginia | United States | ||
| 47 | Norfolk | Virginia | United States | 23502 | |
| 48 | Richmond | Virginia | United States | ||
| 49 | Seattle | Washington | United States | ||
| 50 | San Juan | Puerto Rico | 00927 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Anu M Osinusi, MD, MPH, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
Responsible Party:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02201901
Other Study ID Numbers:
- GS-US-342-1137
First Posted:
Jul 28, 2014
Last Update Posted:
Nov 15, 2018
Last Verified:
Oct 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 a total of 47 study sites in the United States. The first participant was screened on 31 July 2014. The last study visit occurred on 25 November 2015. |
|---|---|
| Pre-assignment Detail | 438 participants were screened. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (Sofosbuvir/velpatasvir) (400/100 mg) fixed dose combination (FDC) tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + Ribavirin (RBV) tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Period Title: Overall Study | |||
| STARTED | 90 | 88 | 90 |
| COMPLETED | 75 | 79 | 77 |
| NOT COMPLETED | 15 | 9 | 13 |
Baseline Characteristics
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks ((Group 3) | Total |
|---|---|---|---|---|
| Arm/Group Description | SOF/VEL (Sofosbuvir/velpatasvir) (400/100 mg) fixed dose combination (FDC) tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + Ribavirin (RBV) tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks | Total of all reporting groups |
| Overall Participants | 90 | 87 | 90 | 267 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
58
(6.3)
|
58
(6.9)
|
58
(5.8)
|
58
(6.3)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
33
36.7%
|
21
24.1%
|
27
30%
|
81
30.3%
|
| Male |
57
63.3%
|
66
75.9%
|
63
70%
|
186
69.7%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
13
14.4%
|
13
14.9%
|
13
14.4%
|
39
14.6%
|
| Not Hispanic or Latino |
77
85.6%
|
74
85.1%
|
77
85.6%
|
228
85.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (participants) [Number] | ||||
| Black or African American |
6
6.7%
|
5
5.7%
|
6
6.7%
|
17
6.4%
|
| White |
79
87.8%
|
79
90.8%
|
81
90%
|
239
89.5%
|
| Asian |
3
3.3%
|
0
0%
|
2
2.2%
|
5
1.9%
|
| American Indian or Alaska Native |
0
0%
|
1
1.1%
|
0
0%
|
1
0.4%
|
| Native Hawaiian or Pacific Islander |
0
0%
|
1
1.1%
|
0
0%
|
1
0.4%
|
| Other |
2
2.2%
|
1
1.1%
|
0
0%
|
3
1.1%
|
| Not Disclosed |
0
0%
|
0
0%
|
1
1.1%
|
1
0.4%
|
| HCV RNA Category (participants) [Number] | ||||
| < 800,000 IU/mL |
31
34.4%
|
42
48.3%
|
45
50%
|
118
44.2%
|
| ≥ 800,000 IU/mL |
59
65.6%
|
45
51.7%
|
45
50%
|
149
55.8%
|
| HCV RNA (log 10 IU/mL) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [log 10 IU/mL] |
6.0
(0.54)
|
5.8
(0.61)
|
5.9
(0.63)
|
5.9
(0.60)
|
| HCV Genotype (participants) [Number] | ||||
| Genotype 1 |
68
75.6%
|
68
78.2%
|
71
78.9%
|
207
77.5%
|
| Genotype 2 |
4
4.4%
|
4
4.6%
|
4
4.4%
|
12
4.5%
|
| Genotype 3 |
14
15.6%
|
13
14.9%
|
12
13.3%
|
39
14.6%
|
| Genotype 4 |
4
4.4%
|
2
2.3%
|
2
2.2%
|
8
3%
|
| Genotype 6 |
0
0%
|
0
0%
|
1
1.1%
|
1
0.4%
|
| IL28B (participants) [Number] | ||||
| CC |
20
22.2%
|
22
25.3%
|
20
22.2%
|
62
23.2%
|
| CT |
51
56.7%
|
46
52.9%
|
49
54.4%
|
146
54.7%
|
| TT |
19
21.1%
|
19
21.8%
|
19
21.1%
|
57
21.3%
|
| Missing |
0
0%
|
0
0%
|
2
2.2%
|
2
0.7%
|
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) 12 weeks following the last dose of study drug. |
| Time Frame | Posttreatment Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Full Analysis Set (FAS): participants who were randomized into the study and received at least 1 dose of study drug. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| Number (95% Confidence Interval) [percentage of participants] |
83.3
92.6%
|
94.3
108.4%
|
87.8
97.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | SOF/VEL 12 Weeks (Group 1) |
|---|---|---|
| Comments | A sample size of 75 participants per treatment group would provide over 99% power to detect 40% improvement in SVR12 rate from the assumed spontaneous rate of 1% or less using a 2-sided exact 1-sample binomial test at significance level of 0.0167. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Binomial test | |
| Comments | P-value is from the 2-sided exact 1-sample binomial test for the superiority of SOF/VEL 12 weeks (Group 1) over prespecified rate of 1% . | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | SOF/VEL+RBV 12 Weeks (Group 2) |
|---|---|---|
| Comments | A sample size of 75 participants per treatment group would provide over 99% power to detect 40% improvement in SVR12 rate from the assumed spontaneous rate of 1% or less using a 2-sided exact 1-sample binomial test at significance level of 0.0167. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Binomial test | |
| Comments | P-value is from the 2-sided exact 1-sample binomial test for the superiority of SOF/VEL+RBV 12 weeks (Group 2) over prespecified rate of 1%. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|
| Comments | A sample size of 75 participants per treatment group would provide over 99% power to detect 40% improvement in SVR12 rate from the assumed spontaneous rate of 1% or less using a 2-sided exact 1-sample binomial test at significance level of 0.0167. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Binomial test | |
| Comments | P-value is from the 2-sided exact 1-sample binomial test for the superiority of SOF/VEL 24 weeks (Group 3) over prespecified rate of 1%. | |
| Title | Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event |
|---|---|
| Description | |
| Time Frame | Up to 24 weeks plus 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| Number [percentage of participants] |
1.1
1.2%
|
16.1
18.5%
|
4.4
4.9%
|
| Title | Percentage of Participants With Sustained Virologic Response 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) |
|---|---|
| Description | SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively. |
| Time Frame | Posttreatment Weeks 4 and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| SVR4 |
92.2
102.4%
|
95.4
109.7%
|
90.0
100%
|
| SVR24 |
83.3
92.6%
|
94.3
108.4%
|
87.8
97.6%
|
| Title | Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |
|---|---|
| Description | |
| Time Frame | Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| Wk 1(Group 1: N=90; Group 2: N=87; Group 3: N=90) |
2.2
2.4%
|
14.9
17.1%
|
11.1
12.3%
|
| Wk 2 (Group 1: N=90; Group 2: N=87;Group 3: N=89) |
34.4
38.2%
|
49.4
56.8%
|
39.3
43.7%
|
| Wk 4 (Group 1: N=90; Group 2: N=87; Group 3: N=89) |
81.1
90.1%
|
80.5
92.5%
|
91.0
101.1%
|
| Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88) |
98.9
109.9%
|
97.6
112.2%
|
98.9
109.9%
|
| Wk 8(Group 1: N=89; Group 2: N=84; Group 3: N=87) |
98.9
109.9%
|
98.8
113.6%
|
100.0
111.1%
|
| Wk 10(Group 1: N=89; Group 2: N=84; Group 3: N=87) |
100.0
111.1%
|
98.8
113.6%
|
100.0
111.1%
|
| Wk 12(Group 1: N=89; Group 2: N=83; Group 3: N=87) |
100.0
111.1%
|
98.8
113.6%
|
97.7
108.6%
|
| Wk 16(Group 1: N=0; Group 2: N=0; Group 3: N=86) |
NA
NaN
|
NA
NaN
|
97.7
108.6%
|
| Wk 20(Group 1: N=0; Group 2: N=0;Group 3: N=84) |
NA
NaN
|
NA
NaN
|
100.0
111.1%
|
| Wk 24(Group 1: N=0; Group 2: N=0; Group 3: N=84) |
NA
NaN
|
NA
NaN
|
100.0
111.1%
|
| Title | Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |
|---|---|
| Description | |
| Time Frame | Baseline; Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| Wk 1(Group 1: N=89; Group 2: N=83; Group 3: N=88) |
-3.51
(0.652)
|
-3.63
(0.691)
|
-3.72
(0.680)
|
| Wk 2(Group 1: N=89; Group 2: N=87; Group 3: N=88) |
-4.24
(0.677)
|
-4.17
(0.647)
|
-4.38
(0.669)
|
| Wk 4(Group 1: N=88; Group 2: N=86; Group 3: N=88) |
-4.78
(0.549)
|
-4.58
(0.568)
|
-4.70
(0.613)
|
| Wk 6(Group 1: N=89; Group 2: N=85; Group 3: N=88) |
-4.87
(0.536)
|
-4.68
(0.607)
|
-4.74
(0.630)
|
| Wk 8(Group 1: N=89; Group 2: N=83; Group 3: N=87) |
-4.87
(0.536)
|
-4.68
(0.622)
|
-4.76
(0.613)
|
| Wk 10(Group 1: N=89; Group 2: N=84; Group 3, N=87) |
-4.87
(0.536)
|
-4.67
(0.634)
|
-4.76
(0.613)
|
| Wk 12(Group 1: N=89; Group 2: N=82; Group 3: N=86) |
-4.87
(0.536)
|
-4.68
(0.624)
|
-4.75
(0.618)
|
| Wk 16 (Group 1: N=0; Group 2: N=0; Group 3: N=85) |
NA
(NA)
|
NA
(NA)
|
-4.76
(0.617)
|
| Wk 20 (Group 1: N=0; Group 2: N=0; Group 3: N =84) |
NA
(NA)
|
NA
(NA)
|
-4.77
(0.613)
|
| Wk 24 (Group 1: N=0; Group 2: N=0; Group 3: N =84) |
NA
(NA)
|
NA
(NA)
|
-4.77
(0.613)
|
| Title | Percentage of Participants With Virologic Failure |
|---|---|
| Description | Virologic failure was defined as On-treatment virologic failure HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, HCV RNA persistently ≥ LLOQ through 8 weeks of treatment (ie nonresponse) Relapse 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 90 | 87 | 90 |
| Number (95% Confidence Interval) [percentage of participants] |
12.2
13.6%
|
3.4
3.9%
|
8.9
9.9%
|
| Title | Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in MELD Score |
|---|---|
| Description | Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease. |
| Time Frame | Baseline to Posttreatment Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 69 | 75 | 69 |
| Decrease (Improvement) |
55.1
61.2%
|
49.3
56.7%
|
50.7
56.3%
|
| No Change |
20.3
22.6%
|
25.3
29.1%
|
21.7
24.1%
|
| Increase (Worsening) |
24.6
27.3%
|
25.3
29.1%
|
27.5
30.6%
|
| Title | Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 24 in Child-Pugh-Turcotte (CPT) Score |
|---|---|
| Description | CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15; higher scores/increased scores indicate greater severity of disease. |
| Time Frame | Baseline to Posttreatment Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set with available data were analyzed. |
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) |
|---|---|---|---|
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks |
| Measure Participants | 69 | 75 | 69 |
| Decrease (Improvement) |
44.9
49.9%
|
53.3
61.3%
|
63.8
70.9%
|
| No Change |
43.5
48.3%
|
37.3
42.9%
|
27.5
30.6%
|
| Increase (Worsening) |
11.6
12.9%
|
9.3
10.7%
|
8.7
9.7%
|
Adverse Events
| Time Frame | Up to 24 weeks plus 30 days | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set | |||||
| Arm/Group Title | SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) | |||
| Arm/Group Description | SOF/VEL (400/100 mg) FDC tablet once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet + RBV tablets (1000 or 1200 mg/day divided twice daily) administered orally once daily for 12 weeks | SOF/VEL (400/100 mg) FDC tablet once daily for 24 weeks | |||
All Cause Mortality |
||||||
| SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/90 (18.9%) | 14/87 (16.1%) | 16/90 (17.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/90 (1.1%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Iron deficiency anaemia | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Atrial fibrillation | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Myocardial infarction | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Endocrine disorders | ||||||
| Adrenal insufficiency | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Gastrointestinal disorders | ||||||
| Ascites | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Colitis | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Duodenal ulcer perforation | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Gastric ulcer | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Gastric varices haemorrhage | 1/90 (1.1%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Gastrointestinal haemorrhage | 3/90 (3.3%) | 0/87 (0%) | 0/90 (0%) | |||
| Haematemesis | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Ileus | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Incarcerated umbilical hernia | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Mallory-Weiss syndrome | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Nausea | 2/90 (2.2%) | 0/87 (0%) | 0/90 (0%) | |||
| Rectal haemorrhage | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Small intestinal obstruction | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Upper gastrointestinal haemorrhage | 1/90 (1.1%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Vomiting | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| General disorders | ||||||
| Hernia | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Hepatobiliary disorders | ||||||
| Hepatorenal syndrome | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Hyperbilirubinaemia | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Jaundice | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Portal vein thrombosis | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Infections and infestations | ||||||
| Bacteraemia | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Bone abscess | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Cellulitis | 1/90 (1.1%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Device related infection | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Escherichia infection | 0/90 (0%) | 1/87 (1.1%) | 1/90 (1.1%) | |||
| Infectious colitis | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Localised infection | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Osteomyelitis | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Peritonitis | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Pneumonia | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Sepsis | 1/90 (1.1%) | 3/87 (3.4%) | 1/90 (1.1%) | |||
| Urinary tract infection | 0/90 (0%) | 2/87 (2.3%) | 0/90 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Head injury | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Hip fracture | 0/90 (0%) | 1/87 (1.1%) | 1/90 (1.1%) | |||
| Joint dislocation | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Radius fracture | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Rib fracture | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Splenic rupture | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Tibia fracture | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Traumatic haemothorax | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperkalaemia | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Hyponatraemia | 1/90 (1.1%) | 2/87 (2.3%) | 0/90 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Rhabdomyolysis | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Diffuse large B-cell lymphoma | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Hepatocellular carcinoma | 0/90 (0%) | 0/87 (0%) | 3/90 (3.3%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Hepatic encephalopathy | 2/90 (2.2%) | 2/87 (2.3%) | 1/90 (1.1%) | |||
| Seizure | 1/90 (1.1%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Syncope | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Psychiatric disorders | ||||||
| Depression | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Mental status changes | 1/90 (1.1%) | 0/87 (0%) | 0/90 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Hypoxia | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Pleural effusion | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Pulmonary hypertension | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Respiratory failure | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Skin ulcer | 0/90 (0%) | 1/87 (1.1%) | 0/90 (0%) | |||
| Vascular disorders | ||||||
| Hypotension | 0/90 (0%) | 0/87 (0%) | 1/90 (1.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| SOF/VEL 12 Weeks (Group 1) | SOF/VEL+RBV 12 Weeks (Group 2) | SOF/VEL 24 Weeks (Group 3) | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 65/90 (72.2%) | 74/87 (85.1%) | 61/90 (67.8%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 4/90 (4.4%) | 26/87 (29.9%) | 3/90 (3.3%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 1/90 (1.1%) | 5/87 (5.7%) | 3/90 (3.3%) | |||
| Abdominal pain | 7/90 (7.8%) | 6/87 (6.9%) | 4/90 (4.4%) | |||
| Ascites | 5/90 (5.6%) | 4/87 (4.6%) | 0/90 (0%) | |||
| Constipation | 6/90 (6.7%) | 3/87 (3.4%) | 6/90 (6.7%) | |||
| Diarrhoea | 6/90 (6.7%) | 18/87 (20.7%) | 7/90 (7.8%) | |||
| Gastrooesophageal reflux disease | 2/90 (2.2%) | 2/87 (2.3%) | 8/90 (8.9%) | |||
| Nausea | 20/90 (22.2%) | 22/87 (25.3%) | 18/90 (20%) | |||
| Vomiting | 7/90 (7.8%) | 5/87 (5.7%) | 6/90 (6.7%) | |||
| General disorders | ||||||
| Fatigue | 23/90 (25.6%) | 34/87 (39.1%) | 21/90 (23.3%) | |||
| Oedema peripheral | 7/90 (7.8%) | 6/87 (6.9%) | 7/90 (7.8%) | |||
| Pyrexia | 6/90 (6.7%) | 4/87 (4.6%) | 3/90 (3.3%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 2/90 (2.2%) | 3/87 (3.4%) | 8/90 (8.9%) | |||
| Upper respiratory tract infection | 3/90 (3.3%) | 2/87 (2.3%) | 8/90 (8.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 4/90 (4.4%) | 2/87 (2.3%) | 5/90 (5.6%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 7/90 (7.8%) | 3/87 (3.4%) | 2/90 (2.2%) | |||
| Back pain | 6/90 (6.7%) | 1/87 (1.1%) | 4/90 (4.4%) | |||
| Muscle spasms | 3/90 (3.3%) | 10/87 (11.5%) | 4/90 (4.4%) | |||
| Nervous system disorders | ||||||
| Headache | 23/90 (25.6%) | 18/87 (20.7%) | 17/90 (18.9%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 9/90 (10%) | 12/87 (13.8%) | 9/90 (10%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 2/90 (2.2%) | 9/87 (10.3%) | 0/90 (0%) | |||
| Dyspnoea | 4/90 (4.4%) | 8/87 (9.2%) | 2/90 (2.2%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 10/90 (11.1%) | 4/87 (4.6%) | 4/90 (4.4%) | |||
| Rash | 6/90 (6.7%) | 5/87 (5.7%) | 7/90 (7.8%) | |||
| Vascular disorders | ||||||
| Hypertension | 3/90 (3.3%) | 5/87 (5.7%) | 0/90 (0%) | |||
Limitations/Caveats
There were no limitations affecting the analysis or results.
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:
NCT02201901
Other Study ID Numbers:
- GS-US-342-1137
First Posted:
Jul 28, 2014
Last Update Posted:
Nov 15, 2018
Last Verified:
Oct 1, 2016