Clinical Trial Results:
A Phase 3, Global, Multicenter, Randomized, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination for 12 Weeks and Sofosbuvir/Velpatasvir for 12 Weeks in Direct-Acting Antiviral-Experienced Subjects with Chronic HCV Infection who Have Not Received an NS5A Inhibitor
Summary
|
|
EudraCT number |
2015-003167-10 |
Trial protocol |
DE FR GB |
Global end of trial date |
18 Jan 2017
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
01 Feb 2018
|
First version publication date |
01 Feb 2018
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
GS-US-367-1170
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02639247 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Gilead Sciences
|
||
Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
|
||
Public contact |
Clinical Trials Mailbox, Gilead Sciences International Ltd., GileadClinicalTrials@gilead.com
|
||
Scientific contact |
Clinical Trials Mailbox, Gilead Sciences International Ltd., GileadClinicalTrials@gilead.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
18 Jan 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
05 Oct 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
18 Jan 2017
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
The primary objective of the study was to evaluate the efficacy, safety, and tolerability of treatment with sofosbuvir/velpatasvir/voxilaprevir (Vosevi®; SOF/VEL/VOX) fixed-dose combination (FDC) for 12 weeks and of sofosbuvir/velpatasvir (Epclusa®; SOF/VEL) FDC for 12 weeks in direct-acting antiviral (DAA)-experienced adults with chronic hepatitis C virus (HCV) infection with or without cirrhosis who have not received prior treatment with a regimen containing an inhibitor of the HCV NS5A protein.
|
||
Protection of trial subjects |
The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements.
This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Dec 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 12
|
||
Country: Number of subjects enrolled |
France: 45
|
||
Country: Number of subjects enrolled |
Germany: 24
|
||
Country: Number of subjects enrolled |
Canada: 38
|
||
Country: Number of subjects enrolled |
Australia: 23
|
||
Country: Number of subjects enrolled |
United States: 188
|
||
Country: Number of subjects enrolled |
New Zealand: 3
|
||
Worldwide total number of subjects |
333
|
||
EEA total number of subjects |
81
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
284
|
||
From 65 to 84 years |
48
|
||
85 years and over |
1
|
|
|||||||||||||||||||||||||
Recruitment
|
|||||||||||||||||||||||||
Recruitment details |
Participants were enrolled across 101 study sites in North America, Europe, and Asia Pacific. The first participant was screened on 23 December 2015. The last study visit occurred on 18 January 2017. | ||||||||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||||||||
Screening details |
397 participants were screened. | ||||||||||||||||||||||||
Period 1
|
|||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
|
|||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||||||||
Arm title
|
SOF/VEL/VOX 12 Weeks | ||||||||||||||||||||||||
Arm description |
SOF/VEL/VOX (400/100/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
SOF/VEL/VOX
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
Vosevi®, GS-7977/GS-5816/GS-9857
|
||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
400/100/100 mg FDC tablet administered orally once daily with food
|
||||||||||||||||||||||||
Arm title
|
SOF/VEL 12 Weeks | ||||||||||||||||||||||||
Arm description |
SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
SOF/VEL
|
||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||
Other name |
Epclusa®, GS-7977/GS-5816
|
||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||
Dosage and administration details |
400/100 mg FDC tablet administered orally once daily without regard to food
|
||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL/VOX 12 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SOF/VEL/VOX (400/100/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL 12 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
SOF/VEL/VOX 12 Weeks
|
||
Reporting group description |
SOF/VEL/VOX (400/100/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks | ||
Reporting group title |
SOF/VEL 12 Weeks
|
||
Reporting group description |
SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks |
|
|||||||||||||
End point title |
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [1] | ||||||||||||
End point description |
SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment. Full Analysis Set (FAS) included all randomized or enrolled participants who took at least 1 dose of study drug.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Posttreatment Week 12
|
||||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The statistical analysis of this primary endpoint is provided in the attachment. |
|||||||||||||
|
|||||||||||||
Attachments |
Primary_Endpoint_StatsAnalysis |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event [2] | ||||||||||||
End point description |
Safety Analysis Set included participants who took at least 1 dose of study drug.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
Up to 12 weeks
|
||||||||||||
Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned or performed. |
|||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) | ||||||||||||||||||
End point description |
SVR4 and SVR24 are defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively. Full Analysis Set.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Posttreatment Weeks 4 and 24
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Percentage of Participants With HCV RNA < LLOQ On Treatment | |||||||||||||||||||||||||||
End point description |
Full Analysis Set
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Weeks 1, 2, 4, 8 and 12
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
Change From Baseline in HCV RNA | |||||||||||||||||||||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Weeks 1, 2, 4, 8, and 12
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants With Virologic Failure | ||||||||||||
End point description |
- 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.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to Posttreatment Week 24
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 12 weeks plus 30 days
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety Analysis Set: all participants who received at least 1 dose of study drug
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL/VOX 12 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SOF/VEL/VOX (400/100/100 mg) fixed-dose combination (FDC) tablet orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
SOF/VEL 12 Weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
SOF/VEL (400/100 mg) FDC tablet orally once daily for 12 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |