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Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 12 Weeks in Adults With Chronic Genotype 2 HCV Infection (ASTRAL-2)

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ClinicalTrials.gov Identifier: NCT02220998
Recruitment Status : Completed
First Posted : August 20, 2014
Results First Posted : November 15, 2016
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Interventions Drug: SOF/VEL
Drug: SOF
Drug: RBV
Enrollment 269
Recruitment Details Participants were enrolled at study sites in the United States. The first participant was screened on 22 September 2014. The last study visit occurred on 03 September 2015.
Pre-assignment Details 317 participants were screened.
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description Sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet administered orally once daily for 12 weeks Sofosbuvir (SOF) 400 mg tablet administered orally once daily + ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Period Title: Overall Study
Started 135 134
Completed 128 123
Not Completed 7 11
Reason Not Completed
Randomized but Never Treated             1             2
Death             2             0
Lack of Efficacy             0             5
Lost to Follow-up             4             4
Arm/Group Title SOF/VEL SOF+RBV Total
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 134 132 266
Hide Baseline Analysis Population Description
Safety Analysis Set: participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 134 participants 132 participants 266 participants
57  (10.6) 57  (9.3) 57  (10.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
Female
48
  35.8%
60
  45.5%
108
  40.6%
Male
86
  64.2%
72
  54.5%
158
  59.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
Hispanic or Latino
26
  19.4%
23
  17.4%
49
  18.4%
Not Hispanic or Latino
104
  77.6%
107
  81.1%
211
  79.3%
Unknown or Not Reported
4
   3.0%
2
   1.5%
6
   2.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
Black or African American 6 12 18
White 124 111 235
Asian 1 5 6
Native Hawaiian or Pacific Islander 0 1 1
Other 1 2 3
Not Disclosed 2 1 3
Cirrhosis Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
Present 19 19 38
Absent 115 112 227
Missing 0 1 1
IL28b Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
CC 55 46 101
CT 61 64 125
TT 18 22 40
[1]
Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.
HCV RNA  
Mean (Standard Deviation)
Unit of measure:  Log10 IU/mL
Number Analyzed 134 participants 132 participants 266 participants
6.5  (0.78) 6.4  (0.74) 6.4  (0.76)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 132 participants 266 participants
< 800,000 IU/mL 23 31 54
≥ 800,000 IU/mL 111 101 212
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: participants randomized or enrolled into the study and received at least 1 dose of study drug.
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.3
(95.9 to 100.0)
93.9
(88.4 to 97.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF/VEL, SOF+RBV
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A sample size of 120 per treatment group provided 90% power to establish non-inferiority in the SVR12 rates between the SOF/VEL group and the SOF+RBV group. It was based on the assumptions that the non-inferiority margin is 10%, both groups have a SVR12 rate of 94%, and the significance level is 0.025 one-sided.
Method of Estimation Estimation Parameter Difference in proportions
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
0.2 to 10.3
Estimation Comments Difference in proportions between treatment groups and associated 95% confidence intervals (CI) are calculated based on stratum-adjusted Mantel-Haenszel proportions.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SOF/VEL, SOF+RBV
Comments The superiority of SOF/VEL for 12 weeks over SOF+RBV for 12 weeks was to be tested if the efficacy of SOF/VEL for 12 weeks was demonstrated to be statistically noninferior to SOF+RBV for 12 weeks (ie, if the lower bound of the 95% CI for the strata-adjusted difference in the proportions between groups was greater than the prespecified noninferiority margin of -10%).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments P-value was stratified by cirrhosis status and prior treatment experience.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
Hide Description [Not Specified]
Time Frame Up to 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Measure Type: Number
Unit of Measure: percentage of participants
0.7 0
3.Secondary Outcome
Title Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SVR4
99.3
(95.9 to 100.0)
96.2
(91.4 to 98.8)
SVR24
99.3
(95.9 to 100.0)
93.9
(88.4 to 97.3)
4.Secondary Outcome
Title Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Description [Not Specified]
Time Frame Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1 (SOF/VEL: N = 133; SOF+RBV: N = 132)
12.8
(7.6 to 19.7)
22.7
(15.9 to 30.8)
Week 2 (SOF/VEL: N = 133; SOF+RBV: N = 132)
57.1
(48.3 to 65.7)
59.8
(51.0 to 68.3)
Week 4 (SOF/VEL: N = 133; SOF+RBV: N = 132)
90.2
(83.9 to 94.7)
90.2
(83.7 to 94.7)
Week 6 (SOF/VEL: N = 133; SOF+RBV: N = 132)
97.7
(93.5 to 99.5)
99.2
(95.9 to 100.0)
Week 8 (SOF/VEL: N = 133; SOF+RBV: N = 132)
100.0
(97.3 to 100.0)
100.0
(97.2 to 100.0)
Week 10 (SOF/VEL: N = 133; SOF+RBV: N = 132)
100.0
(97.3 to 100.0)
100.0
(97.2 to 100.0)
Week 12 (SOF/VEL: N = 133; SOF+RBV: N = 131)
100.0
(97.3 to 100.0)
100.0
(97.2 to 100.0)
5.Secondary Outcome
Title Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Description [Not Specified]
Time Frame Baseline; Weeks 1, 2, 4, 6, 8, 10, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Wk 1 (SOF/VEL: N= 132; SOF+RBV: N= 131) -4.51  (0.666) -4.51  (0.553)
Change at Wk 2 (SOF/VEL: N= 132; SOF+RBV: N= 131) -5.08  (0.761) -5.04  (0.701)
Change at Wk 4 (SOF/VEL: N= 132; SOF+RBV: N= 131) -5.29  (0.781) -5.24  (0.755)
Change at Wk 6 (SOF/VEL: N= 133; SOF+RBV: N= 131) -5.31  (0.781) -5.27  (0.741)
Change at Wk 8 (SOF/VEL: N= 133; SOF+RBV: N= 132) -5.32  (0.782) -5.27  (0.739)
Change at Wk 10 (SOF/VEL: N= 133; SOF+RBV: N= 132) -5.32  (0.782) -5.27  (0.739)
Change at Wk 12 (SOF/VEL: N= 133; SOF+RBV: N= 131) -5.32  (0.782) -5.26  (0.737)
6.Secondary Outcome
Title Percentage of Participants With Virologic Failure
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
Overall Number of Participants Analyzed 134 132
Measure Type: Number
Unit of Measure: percentage of participants
0 4.5
Time Frame Up to 12 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title SOF/VEL SOF+RBV
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks SOF 400 mg tablet administered orally once daily + RBV tablets (1000 or 1200 mg daily based on weight) for 12 weeks
All-Cause Mortality
SOF/VEL SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
SOF/VEL SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   2/134 (1.49%)   2/132 (1.52%) 
Gastrointestinal disorders     
Abdominal pain  1  1/134 (0.75%)  0/132 (0.00%) 
Enteritis  1  1/134 (0.75%)  0/132 (0.00%) 
Infections and infestations     
Pneumonia  1  1/134 (0.75%)  0/132 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/134 (0.00%)  1/132 (0.76%) 
Psychiatric disorders     
Depression  1  0/134 (0.00%)  1/132 (0.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF/VEL SOF+RBV
Affected / at Risk (%) Affected / at Risk (%)
Total   69/134 (51.49%)   84/132 (63.64%) 
Blood and lymphatic system disorders     
Anaemia  1  0/134 (0.00%)  8/132 (6.06%) 
Gastrointestinal disorders     
Abdominal pain  1  5/134 (3.73%)  7/132 (5.30%) 
Nausea  1  14/134 (10.45%)  20/132 (15.15%) 
Vomiting  1  5/134 (3.73%)  8/132 (6.06%) 
General disorders     
Fatigue  1  20/134 (14.93%)  47/132 (35.61%) 
Infections and infestations     
Nasopharyngitis  1  8/134 (5.97%)  2/132 (1.52%) 
Sinusitis  1  7/134 (5.22%)  5/132 (3.79%) 
Upper respiratory tract infection  1  8/134 (5.97%)  5/132 (3.79%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/134 (4.48%)  8/132 (6.06%) 
Back pain  1  2/134 (1.49%)  7/132 (5.30%) 
Nervous system disorders     
Dizziness  1  3/134 (2.24%)  8/132 (6.06%) 
Headache  1  24/134 (17.91%)  29/132 (21.97%) 
Psychiatric disorders     
Anxiety  1  8/134 (5.97%)  8/132 (6.06%) 
Insomnia  1  6/134 (4.48%)  19/132 (14.39%) 
Irritability  1  4/134 (2.99%)  9/132 (6.82%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  6/134 (4.48%)  7/132 (5.30%) 
Rash  1  2/134 (1.49%)  7/132 (5.30%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
EMail: ClinicalTrialDisclosures@gilead.com
Publications of Results:
Asselah T, Charlton M, Feld J, Foster GR, Mcnally J, Brainard DM, et al. The ASTRAL Studies: Evaluation of SOF/GS-5816 Single Tablet Regimen for the Treatment of Genotype 1-6 HCV Infection [Poster P1332]. J Hepatol 2015;62:S855-S6.
Sulkowski, MS., Brau N., Lawitz E., Shiffman ML, Towner WL, Ruane PJ et al. A Randomized Controlled Trial of Sofosbuvir/GS-5816 Fixed Dose Combination for 12 Weeks Compared to Sofosbuvir with Ribavirin for 12 Weeks in Genotype 2 HCV Infected Patients: The Phase 3 ASTRAL-2 Study [Oral 205] Hepatology 2015; 62: 1 (SUPPL) 313A.
Layout table for additonal information
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02220998    
Other Study ID Numbers: GS-US-342-1139
First Submitted: August 18, 2014
First Posted: August 20, 2014
Results First Submitted: July 27, 2016
Results First Posted: November 15, 2016
Last Update Posted: November 15, 2018