Clinical Trial Results:
A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching from an Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fixed-Dose Combination Regimen or a Tenofovir Disoproxil Fumarate Containing Regimen to Fixed-Dose Combination of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Elderly, Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 65 Years
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Summary
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EudraCT number |
2017-003428-61 |
Trial protocol |
GB BE ES FR IT |
Global end of trial date |
29 May 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Nov 2020
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First version publication date |
22 Nov 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GS-US-380-4449
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03405935 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Gilead Sciences
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Sponsor organisation address |
333 Lakeside Drive, Foster City, CA, United States, 94404
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Public contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Scientific contact |
Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 May 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Nov 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
29 May 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to characterize the virologic efficacy of switching virologically suppressed participants on an elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) regimen or a tenofovir disoproxil fumarate (TDF) containing regimen to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) FDC.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Mar 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 27
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Country: Number of subjects enrolled |
United Kingdom: 1
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Country: Number of subjects enrolled |
Belgium: 8
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Country: Number of subjects enrolled |
France: 28
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Country: Number of subjects enrolled |
Italy: 22
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Worldwide total number of subjects |
86
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EEA total number of subjects |
86
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
86
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants were enrolled at study sites in Europe. The first participant was screened on 01 March 2018. The last study visit occurred on 29 May 2020. | ||||||||||||||||
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Pre-assignment
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Screening details |
90 participants were screened. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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B/F/TAF | ||||||||||||||||
Arm description |
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablet once daily, without regard to food for at least 96 weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
B/F/TAF
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Investigational medicinal product code |
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Other name |
Biktarvy®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
50/200/25 mg administered once daily for up to Week 96
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Baseline characteristics reporting groups
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Reporting group title |
B/F/TAF
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Reporting group description |
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablet once daily, without regard to food for at least 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
B/F/TAF
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Reporting group description |
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) FDC tablet once daily, without regard to food for at least 96 weeks. | ||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the Food and Drug Administration (FDA)-Defined Snapshot Algorithm [1] | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined timepoint within an allowed window of time, along with study drug discontinuation status. The Full Analysis Set (FAS) included all participants who were enrolled and received at least 1 dose of study drug; and did not have major protocol violations.
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End point type |
Primary
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End point timeframe |
Week 24
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| 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: No statistical comparison was planned or performed. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Experiencing Adverse Events (AEs) Through Week 24 | ||||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs may also included pre- or post-treatment complications that occurred as a result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting events that increased in severity or changed in nature during or as a consequence of participation in the clinical study were also considered AEs. The Safety Analysis Set included all participants who were enrolled and received at least 1 dose of study drug.
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End point type |
Secondary
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End point timeframe |
First dose date up to Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Experiencing AEs Through Week 48 | ||||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs may also included pre- or post-treatment complications that occurred as a result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting events that increased in severity or changed in nature during or as a consequence of participation in the clinical study were also considered AEs. Participants in the Safety Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
First dose date Up to Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Experiencing AEs Through Week 72 | ||||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs may also included pre- or post-treatment complications that occurred as a result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting events that increased in severity or changed in nature during or as a consequence of participation in the clinical study were also considered AEs. Participants in the Safety Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
First dose date Up to Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants Experiencing AEs Through Week 96 | ||||||||
End point description |
An AE was any untoward medical occurrence in a clinical study participant administered a medicinal product, which did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs may also included pre- or post-treatment complications that occurred as a result of protocol specified procedures, lack of efficacy, overdose, drug abuse/misuse reports, or occupational exposure. Preexisting events that increased in severity or changed in nature during or as a consequence of participation in the clinical study were also considered AEs. Participants in the Safety Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
First dose date Up to Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA-Defined Snapshot Algorithm | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined timepoint within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 72 as Defined by the FDA-Defined Snapshot Algorithm | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 72 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined timepoint within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA-Defined Snapshot Algorithm | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the snapshot algorithm, which defined a participant's virologic response status using only the viral load at the predefined timepoint within an allowed window of time, along with study drug discontinuation status. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Cell Count at Week 24 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Cell Count at Week 48 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Cell Count at Week 72 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Cell Count at Week 96 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Percentage at Week 24 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Percentage at Week 48 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Percentage at Week 72 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in CD4 Percentage at Week 96 | ||||||||
End point description |
Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Analyzed by Missing = Failure Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using missing = failure approach. In this approach, all missing data were treated as HIV-1 RNA ≥ 50 copies/mL. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Analyzed by Missing = Failure Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using missing = failure approach. In this approach, all missing data were treated as HIV-1 RNA ≥ 50 copies/mL. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 72, as Analyzed by Missing = Failure Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 72 was analyzed using missing = failure approach. In this approach, all missing data were treated as HIV-1 RNA ≥ 50 copies/mL. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96, as Analyzed by Missing = Failure Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using missing = failure approach. In this approach, all missing data were treated as HIV-1 RNA ≥ 50 copies/mL. Participants in the Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 96
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24, as Analyzed by Missing = Excluded Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48, as Analyzed by Missing = Excluded Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 48
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 72, as Analyzed by Missing = Excluded Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 72 was analyzed using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 72
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96, as Analyzed by Missing = Excluded Approach | ||||||||
End point description |
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Participants in the Full Analysis Set with available data were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 96
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events: First dose of study drug up to last dose plus 30 days ( up to Week 102.9); All-Cause Mortality: First dose date up to Week 102.9
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Adverse event reporting additional description |
The Safety Analysis Set included all participants who were enrolled and received at least 1 dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
B/F/TAF
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Reporting group description |
B/F/TAF (50/200/25 mg) FDC tablet once daily, without regard to food for at least 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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03 Jan 2018 |
- Added biomarker blood sample evaluation: A portion of the biomarker blood sample obtained at Day 1, Weeks 4, 12, 24, and 48 may be utilized to assess study drug pharmacokinetics (PK). This will be a random sample with the date and time of the participant's last medication dose recorded.
- 3 inclusion criteria were added: 1) Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 * upper limit of normal (ULN); 2) Total bilirubin ≤ 1.5 * ULN or normal direct bilirubin; 3) Adequate hematologic function (absolute neutrophil count ≥ 750/mm^3 [≥ 0.75 GI/L], platelets ≥ 50,000/mm^3 [≥ 50 GI/L], and hemoglobin ≥ 8.5 g/dL [≥ 85 g/L])
- Concomitant Medication table was modified to be in alignment with the Package Insert for the drug.
- Medical history information collected at screening visit was modified.
- Development of active tuberculosis infection was added to the criteria for discontinuation of study treatment.
- A section on Hepatitis C Management was added.
- Safety data collection was clarified.
- Statistical clarification was provided for the efficacy analyses. |
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18 Dec 2018 |
- All applicable text was revised to reflect study treatment duration change from Week 48 to Week 96.
- Prior and Concomitant Medications and Exclusion Criteria tables were updated for consistency and to ensure that the latest disallowed drug information was included.
- Study GS-US-311-1717 was added to the list of relevant studies. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
