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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

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ClinicalTrials.gov Identifier: NCT01967940
Recruitment Status : Completed
First Posted : October 23, 2013
Results First Posted : June 12, 2017
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE October 18, 2013
First Posted Date  ICMJE October 23, 2013
Results First Submitted Date  ICMJE May 9, 2017
Results First Posted Date  ICMJE June 12, 2017
Last Update Posted Date November 16, 2018
Actual Study Start Date  ICMJE October 25, 2013
Actual Primary Completion Date May 21, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2017)
Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 [ Time Frame: Day 10 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
Proportion of participants with plasma HIV-1 RNA decreases from baseline exceeding 0.5 log10 copies/mL at Day 10 (Part 1) [ Time Frame: Day 10 ]
Change History Complete list of historical versions of study NCT01967940 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2018)
  • Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10 [ Time Frame: Baseline; Day 10 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
  • 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 ]
    The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
  • 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 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
  • 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 ]
    The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
  • Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24 [ Time Frame: Baseline; Week 24 ]
  • Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Part 2: Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline; Week 24 ]
  • Part 2: Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Part 2: Change From Baseline in CD4+ Percentage at Week 24 [ Time Frame: Baseline; Week 24 ]
  • Part 2: Change From Baseline in CD4+ Percentage at Week 48 [ Time Frame: Baseline; Week 48 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2013)
  • Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 10 (Part 1) [ Time Frame: Day 10 ]
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 24 [ Time Frame: Week 24 ]
  • Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Change from baseline in CD4+ cell count (cells/µL) and percentage at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Safety of E/C/F/TAF STR measured by incidence of adverse events and monitoring of laboratory parameters from baseline to Weeks 24 and 48 [ Time Frame: Baseline to Week 24 and 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 3, Two-Part Study to Evaluate the 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
Brief Summary

The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2.

Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen.

In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a > 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Part 1 (Sentinel Cohort followed by a Randomized Cohort), 14-day washout period, then Part 2
Masking: Double (Participant, Investigator)
Masking Description:
Part 1 Sentinel Cohort: Open-label, non-randomized Part 1 Randomized Cohort: Double-blind, randomized Part 2: Open-label, non-randomized
Primary Purpose: Treatment
Condition  ICMJE
  • HIV
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
Intervention  ICMJE
  • Drug: TAF
    25 mg tablet administered orally once daily with food
    Other Names:
    • Vemlidy®
    • GS-7340
  • Drug: Placebo
    Tablets to match TAF administered orally once daily with food
  • Drug: E/C/F/TAF
    150/150/200/10 mg STR administered orally once daily with food
    Other Name: Genvoya®
  • Drug: Current failing ARV regimen
    Participants will continue taking their current ARV regimen as prescribed in Part 1.
  • Drug: ATV
    300 mg tablet administered orally once daily.
    Other Name: Reyataz®
Study Arms  ICMJE
  • Experimental: Part 1 Sentinel Cohort (TAF)
    TAF + their current failing ARV regimen for 10 days in Part 1
    Interventions:
    • Drug: TAF
    • Drug: Current failing ARV regimen
  • Experimental: Part 1 Randomized Cohort (TAF)
    Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive TAF + their current failing ARV regimen for 10 days in Part 1.
    Interventions:
    • Drug: TAF
    • Drug: Current failing ARV regimen
  • Placebo Comparator: Part 1 Randomized Cohort (Placebo)
    Following review of safety and efficacy data from the Sentinel Cohort, participants will be randomized to receive placebo + their current failing ARV regimen for 10 days in Part 1.
    Interventions:
    • Drug: Placebo
    • Drug: Current failing ARV regimen
  • Experimental: Part 2 E/C/F/TAF+ATV
    Following a 14-day period to confirm eligibility, participants in the Randomized Cohort TAF group with a > 0.5 log10 decline in HIV-1 RNA and all participants completing the Randomized Cohort Placebo group will receive E/C/F/TAF+ATV for 48 weeks in Part 2. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.
    Interventions:
    • Drug: E/C/F/TAF
    • Drug: ATV
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 20, 2016)
55
Original Estimated Enrollment  ICMJE
 (submitted: October 18, 2013)
100
Actual Study Completion Date  ICMJE July 31, 2017
Actual Primary Completion Date May 21, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • Currently taking a failing ARV regimen
  • Plasma HIV-1 RNA ≥ 500 copies/mL but ≤ 100,000 copies/mL at screening
  • Normal ECG
  • Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
  • Alanine aminotransferase (AST)/aspartate aminotransferase (AST) ≤ 5 × the upper limit of the normal range (ULN)
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Adequate hematologic function
  • Serum amylase ≤ 5 × ULN
  • Females may enter the study if it is confirmed that she is:

    • Not pregnant or nursing
    • Of non-childbearing potential (ie, have had a hysterectomy, both ovaries removed, medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation [for ≥ 12 months] of previously occurring menses), or
    • Of childbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following study drug dosing

      • Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
  • Males must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
  • Males must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Key Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Hepatitis B surface antigen (HBsAg) positive
  • Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll)
  • History of integrase inhibitor use
  • Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs.
  • Screening or historical genotype report shows resistance to integrase inhibitors
  • Individuals experiencing decompensated cirrhosis
  • Current alcohol or substance use
  • History of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Part 1, Day 1 and must not be anticipated to require systemic therapy during the study.
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Part 1, Day 1
  • Any other clinical condition or prior therapy that would make the individual unsuitable for the study or unable to comply with dosing requirements
  • Participation in any other clinical trial (including observational trials) without prior approval from the sponsor is prohibited while participating in this trial
  • Receiving ongoing therapy with any disallowed medications, including any drugs not to be used with elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide or known allergies to the excipients of E/C/F/TAF STR

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Dominican Republic,   Russian Federation,   Thailand,   Uganda,   United States
Removed Location Countries Australia,   Canada,   Germany,   Poland,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01967940
Other Study ID Numbers  ICMJE GS-US-292-0117
2013-002830-19 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: http://www.gilead.com/research/disclosure-and-transparency
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP