ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01967940
Recruitment Status : Completed
First Posted : October 23, 2013
Results First Posted : June 12, 2017
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: HIV
HIV Infections
Acquired Immunodeficiency Syndrome
Interventions: Drug: TAF
Drug: Placebo
Drug: E/C/F/TAF
Drug: Current failing ARV regimen
Drug: ATV

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled at study sites in the United States, Uganda, Thailand, Russian Federation, and Dominican Republic. The first participant was screened on 25 October 2013. The last study visit occurred on 31 July 2017.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
259 participants were screened.

Reporting Groups
  Description
Part 1 Sentinel Cohort TAF Tenofovir alafenamide (TAF) 25 mg tablet once daily + their current failing regimen for 10 days
Part 1 Randomized Cohort TAF TAF 25 mg tablet once daily + their current failing regimen for 10 days
Part 1 Randomized Cohort Placebo Placebo once daily + their current failing regimen for 10 days
Part 2 E/C/F/TAF + ATV Following a 14 day washout period, participants from the Randomized Cohort TAF group who had a > 0.5 log10 decline in HIV-1 RNA and participants from the Randomized Cohort Placebo group were eligible to receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) (150/150/200/10 mg) single-tablet regimen (STR) plus atazanavir (ATV) 300 mg once daily for 48 weeks. After completion of Part 2, all participants were eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF became commercially available, or until Gilead Sciences terminated development of E/C/F/TAF in the applicable country.

Participant Flow for 2 periods

Period 1:   Part 1
    Part 1 Sentinel Cohort TAF   Part 1 Randomized Cohort TAF   Part 1 Randomized Cohort Placebo   Part 2 E/C/F/TAF + ATV
STARTED   12   28   15   0 
COMPLETED   12   28   15   0 
NOT COMPLETED   0   0   0   0 

Period 2:   Part 2
    Part 1 Sentinel Cohort TAF   Part 1 Randomized Cohort TAF   Part 1 Randomized Cohort Placebo   Part 2 E/C/F/TAF + ATV
STARTED   0 [1]   0 [2]   0 [3]   38 [4] 
COMPLETED   0   0   0   35 
NOT COMPLETED   0   0   0   3 
Enrolled in Part 2 and Never Treated                0                0                0                1 
Adverse Event                0                0                0                1 
Unknown Reason                0                0                0                1 
[1] 4 participants completed Part 1 and did not enter Part 2; 8 participants moved to the Part 2 group
[2] 12 participants completed Part 1 and did not enter Part 2; 16 participants moved to the Part 2 group
[3] 1 participant completed Part 1 and did not enter Part 2; 14 participants moved to the Part 2 group
[4] 38 participants from the Part 1 groups moved to this Part 2 E/C/F/TAF + ATV group



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set: participants who enrolled into Part 1 of the study and received at least one dose of study drug in Part 1.

Reporting Groups
  Description
Part 1 Sentinel Cohort TAF TAF 25 mg tablet once daily + their current failing regimen for 10 days
Part 1 Randomized Cohort TAF TAF 25 mg tablet once daily + their current failing regimen for 10 days
Part 1 Randomized Cohort Placebo Placebo once daily + their current failing regimen for 10 days
Total Total of all reporting groups

Baseline Measures
   Part 1 Sentinel Cohort TAF   Part 1 Randomized Cohort TAF   Part 1 Randomized Cohort Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 12   28   15   55 
Age 
[Units: Years]
Mean (Standard Deviation)
 38  (7.3)   40  (9.1)   43  (8.2)   40  (8.6) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      3  25.0%      16  57.1%      4  26.7%      23  41.8% 
Male      9  75.0%      12  42.9%      11  73.3%      32  58.2% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
       
Hispanic or Latino      5  41.7%      0   0.0%      1   6.7%      6  10.9% 
Not Hispanic or Latino      7  58.3%      28 100.0%      14  93.3%      49  89.1% 
Unknown or Not Reported      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
Asian   0   5   5   10 
Black   3   22   9   34 
White   4   1   0   5 
Other   5   0   1   6 
Region of Enrollment 
[Units: Participants]
       
Russian Federation   2   1   0   3 
United States   5   3   0   8 
Dominican Republic   5   0   1   6 
Uganda   0   19   9   28 
Thailand   0   5   5   10 
HIV-1 RNA 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.18  (0.648)   4.16  (0.544)   4.03  (0.953)   4.13  (0.688) 
HIV-1 RNA Category 
[Units: Participants]
Count of Participants
       
≤ 100,000 copies/mL      12 100.0%      27  96.4%      12  80.0%      51  92.7% 
> 100,000 to ≤ 400,000 copies/mL      0   0.0%      1   3.6%      3  20.0%      4   7.3% 
CD4 Cell Count 
[Units: cells/µL]
Mean (Standard Deviation)
 269  (207.1)   245  (244.6)   232  (162.4)   246  (213.7) 
CD4 Percentage 
[Units: Percentage]
Mean (Standard Deviation)
 17.4  (10.14)   16.5  (11.09)   14.3  (8.61)   16.1  (10.15) 


  Outcome Measures

1.  Primary:   Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10   [ Time Frame: Day 10 ]

2.  Secondary:   Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10   [ Time Frame: Baseline; Day 10 ]

3.  Secondary:   Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24   [ Time Frame: Up to Week 24 ]

4.  Secondary:   Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48   [ Time Frame: Up to Week 48 ]

5.  Secondary:   Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24   [ Time Frame: Up to Week 24 ]

6.  Secondary:   Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48   [ Time Frame: Up to Week 48 ]

7.  Secondary:   Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24   [ Time Frame: Week 24 ]

8.  Secondary:   Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48   [ Time Frame: Week 48 ]

9.  Secondary:   Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24   [ Time Frame: Week 24 ]

10.  Secondary:   Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48   [ Time Frame: Week 48 ]

11.  Secondary:   Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24   [ Time Frame: Baseline; Week 24 ]

12.  Secondary:   Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48   [ Time Frame: Baseline; Week 48 ]

13.  Secondary:   Part 2: Change From Baseline in CD4+ Cell Count at Week 24   [ Time Frame: Baseline; Week 24 ]

14.  Secondary:   Part 2: Change From Baseline in CD4+ Cell Count at Week 48   [ Time Frame: Baseline; Week 48 ]

15.  Secondary:   Part 2: Change From Baseline in CD4+ Percentage at Week 24   [ Time Frame: Baseline; Week 24 ]

16.  Secondary:   Part 2: Change From Baseline in CD4+ Percentage at Week 48   [ Time Frame: Baseline; Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Gilead Clinical Study Information Center
Organization: Gilead Sciences
e-mail: GileadClinicalTrials@gilead.com



Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01967940     History of Changes
Other Study ID Numbers: GS-US-292-0117
2013-002830-19 ( EudraCT Number )
First Submitted: October 18, 2013
First Posted: October 23, 2013
Results First Submitted: May 9, 2017
Results First Posted: June 12, 2017
Last Update Posted: August 16, 2018