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Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Adults With Chronic HCV Infection (ASTRAL-1)

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ClinicalTrials.gov Identifier: NCT02201940
Recruitment Status : Completed
First Posted : July 28, 2014
Results First Posted : September 16, 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatitis C Virus Infection
Interventions Drug: SOF/VEL
Drug: Placebo
Enrollment 741
Recruitment Details Participants were enrolled at study sites in the United States, Canada, Europe, and Asia. The first participant was screened on 18 July 2014. The last study visit occurred on 23 September 2015.
Pre-assignment Details 847 participants were screened.
Arm/Group Title SOF/VEL Placebo
Hide Arm/Group Description Sofosbuvir/velpatasvir (SOF/VEL) (400/100 mg) fixed-dose combination (FDC) tablet administered orally once daily for 12 weeks SOF/VEL placebo tablet administered orally once daily for 12 weeks
Period Title: Overall Study
Started 625 116
Completed 613 0
Not Completed 12 116
Reason Not Completed
Randomized/Enrolled but Never Treated             1             0
Lack of Efficacy             2             113
Lost to Follow-up             5             0
Withdrew Consent             2             1
Investigator's Discretion             1             1
Death             1             0
Adverse Event             0             1
Arm/Group Title SOF/VEL Placebo Total
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks SOF/VEL placebo tablet administered orally once daily for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 624 116 740
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 624 participants 116 participants 740 participants
54  (10.9) 53  (10.4) 54  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Female
250
  40.1%
48
  41.4%
298
  40.3%
Male
374
  59.9%
68
  58.6%
442
  59.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Hispanic or Latino
31
   5.0%
5
   4.3%
36
   4.9%
Not Hispanic or Latino
589
  94.4%
111
  95.7%
700
  94.6%
Unknown or Not Reported
4
   0.6%
0
   0.0%
4
   0.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Black or African American 52 12 64
White 493 89 582
Asian 62 11 73
American Indian/ Alaska Native 7 0 7
Hawaiian or Pacific Islander 1 1 2
Other 6 3 9
Not Disclosed 3 0 3
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Canada 55 7 62
Belgium 40 5 45
United States 234 45 279
China 19 4 23
Italy 16 2 18
United Kingdom 91 13 104
France 126 32 158
Germany 44 8 52
[1]
Measure Description: All randomized participants were analyzed for Region of Enrollment (N = 741).
Cirrhosis Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Present 121 21 142
Absent 501 95 596
Missing 2 0 2
HCV Genotype  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
Genotype 1 328 65 393
Genotype 2 104 21 125
Genotype 4 116 22 138
Genotype 5 35 0 35
Genotype 6 41 8 49
IL28b Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
CC 186 36 222
CT 339 53 392
TT 94 26 120
Missing 5 1 6
[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 624 participants 116 participants 740 participants
6.3  (0.66) 6.3  (0.58) 6.3  (0.65)
HCV RNA Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 624 participants 116 participants 740 participants
< 800,000 IU/mL 163 29 192
≥ 800,000 IU/mL 461 87 548
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 Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.0
(97.9 to 99.6)
0
(0.0 to 3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SOF/VEL
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments Participants in the SOF/VEL group were compared to the performance goal of 85% using a 2-sided exact 1-sample binomial test at the 0.05 significance level.
Method Binomial test
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 Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Measure Type: Number
Unit of Measure: percentage of participants
0.2 1.7
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 Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
SVR4
99.2
(98.1 to 99.7)
0
(0.0 to 3.1)
SVR24
99.0
(97.9 to 99.6)
0
(0.0 to 3.1)
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
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title SOF/VEL Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Week 1 (SOF/VEL: N = 624; Placebo: N = 116)
18.8
(15.8 to 22.0)
0
(0.0 to 3.1)
Week 2 (SOF/VEL: N = 624; Placebo: N = 116)
56.9
(52.9 to 60.8)
0
(0.0 to 3.1)
Week 4 (SOF/VEL: N = 623; Placebo: N = 116)
90.5
(88.0 to 92.7)
0
(0.0 to 3.1)
Week 6 (SOF/VEL: N = 623; Placebo: N = 115)
98.9
(97.7 to 99.5)
0
(0.0 to 3.2)
Week 8 (SOF/VEL: N = 622; Placebo: N = 114)
99.7
(98.8 to 100.0)
0
(0.0 to 3.2)
Week 10 (SOF/VEL: N = 622; Placebo: N = 114)
100.0
(99.4 to 100.0)
0
(0.0 to 3.2)
Week 12 (SOF/VEL: N = 622; Placebo: N = 113)
100.0
(99.4 to 100.0)
0
(0.0 to 3.2)
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 Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Mean (Standard Deviation)
Unit of Measure: log10 IU/mL
Change at Wk 1 (SOF/VEL: N= 617; Placebo: N= 114) -4.29  (0.647) -0.05  (0.561)
Change at Wk 2 (SOF/VEL: N= 622; Placebo: N= 116) -4.82  (0.685) 0.01  (0.280)
Change at Wk 4 (SOF/VEL: N= 617; Placebo: N= 114) -5.08  (0.656) -0.01  (0.297)
Change at Wk 6 (SOF/VEL: N= 623; Placebo: N= 115) -5.11  (0.664) 0.07  (0.298)
Change at Wk 8 (SOF/VEL: N= 622; Placebo: N= 113) -5.11  (0.664) 0.05  (0.281)
Change at Wk 10 (SOF/VEL: N= 622; Placebo: N= 112) -5.12  (0.662) 0.05  (0.337)
Change at Wk 12 (SOF/VEL: N= 622; Placebo: N= 111) -5.12  (0.662) -0.06  (0.580)
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 Placebo
Hide Arm/Group Description:
SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks
SOF/VEL placebo tablet administered orally once daily for 12 weeks
Overall Number of Participants Analyzed 624 116
Measure Type: Number
Unit of Measure: percentage of participants
0.3 100
Time Frame Up to 12 weeks plus 30 days
Adverse Event Reporting Description Safety Analysis Set
 
Arm/Group Title SOF/VEL Placebo
Hide Arm/Group Description SOF/VEL (400/100 mg) FDC tablet administered orally once daily for 12 weeks SOF/VEL placebo tablet administered orally once daily for 12 weeks
All-Cause Mortality
SOF/VEL Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
SOF/VEL Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   15/624 (2.40%)   0/116 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  1/624 (0.16%)  0/116 (0.00%) 
Palpitations  1  1/624 (0.16%)  0/116 (0.00%) 
Gastrointestinal disorders     
Small intestinal obstruction  1  1/624 (0.16%)  0/116 (0.00%) 
General disorders     
Sudden death  1  1/624 (0.16%)  0/116 (0.00%) 
Infections and infestations     
Abscess limb  1  1/624 (0.16%)  0/116 (0.00%) 
Appendicitis  1  1/624 (0.16%)  0/116 (0.00%) 
Bronchitis  1  1/624 (0.16%)  0/116 (0.00%) 
Cellulitis  1  1/624 (0.16%)  0/116 (0.00%) 
Gastroenteritis  1  1/624 (0.16%)  0/116 (0.00%) 
Influenza  1  1/624 (0.16%)  0/116 (0.00%) 
Vestibular neuronitis  1  1/624 (0.16%)  0/116 (0.00%) 
Injury, poisoning and procedural complications     
Ligament sprain  1  1/624 (0.16%)  0/116 (0.00%) 
Upper limb fracture  1  1/624 (0.16%)  0/116 (0.00%) 
Musculoskeletal and connective tissue disorders     
Rotator cuff syndrome  1  1/624 (0.16%)  0/116 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm malignant  1  1/624 (0.16%)  0/116 (0.00%) 
Nervous system disorders     
Epilepsy  1  1/624 (0.16%)  0/116 (0.00%) 
Psychiatric disorders     
Mania  1  1/624 (0.16%)  0/116 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/624 (0.16%)  0/116 (0.00%) 
Vascular disorders     
Extremity necrosis  1  1/624 (0.16%)  0/116 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 18
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SOF/VEL Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   393/624 (62.98%)   77/116 (66.38%) 
Gastrointestinal disorders     
Diarrhoea  1  48/624 (7.69%)  8/116 (6.90%) 
Nausea  1  75/624 (12.02%)  13/116 (11.21%) 
General disorders     
Asthenia  1  42/624 (6.73%)  9/116 (7.76%) 
Fatigue  1  127/624 (20.35%)  24/116 (20.69%) 
Infections and infestations     
Nasopharyngitis  1  80/624 (12.82%)  12/116 (10.34%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  40/624 (6.41%)  9/116 (7.76%) 
Back pain  1  29/624 (4.65%)  11/116 (9.48%) 
Myalgia  1  25/624 (4.01%)  6/116 (5.17%) 
Nervous system disorders     
Headache  1  182/624 (29.17%)  33/116 (28.45%) 
Psychiatric disorders     
Insomnia  1  50/624 (8.01%)  11/116 (9.48%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  39/624 (6.25%)  4/116 (3.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 18
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
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences
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.
Feld JJ, Agarwal K, Hezode C, Asselah T, Ruane PJ, Gruener N, et al. A Phase 3 Double-Blind Placebo-Controlled Evaluation of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Naive and Experienced Genotype 1, 2, 4, 5, 6 HCV Infected Patients with and without Cirrhosis: Results of the ASTRAL-1 Study. J Hepatol 2015;62(6) Suppl:1379A-1380A.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02201940     History of Changes
Other Study ID Numbers: GS-US-342-1138
2014-001683-35 ( EudraCT Number )
First Submitted: July 24, 2014
First Posted: July 28, 2014
Results First Submitted: July 27, 2016
Results First Posted: September 16, 2016
Last Update Posted: November 15, 2018