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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01967940
First received: October 18, 2013
Last updated: May 9, 2017
Last verified: May 2017
October 18, 2013
May 9, 2017
October 25, 2013
May 9, 2016   (Final data collection date for primary outcome measure)
Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10 [ Time Frame: Day 10 ]
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 ]
Complete list of historical versions of study NCT01967940 on ClinicalTrials.gov Archive Site
  • 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 Incidence of Laboratory Parameters and Adverse Events at Weeks 24 and 48 [ Time Frame: Up to 48 weeks ]
  • Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Part 2: Change From Baseline in CD4+ Cell Count (Cells/μL) and Percentage at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
  • Part 2: Pharmacokinetic (PK) Parameter: AUClast of TAF [ Time Frame: Week 4 to Week 12 ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration
  • Part 2: PK Parameter: Clast of TAF [ Time Frame: Week 4 to Week 12 ]
    Clast is defined as the last observable concentration of drug.
  • Part 2: PK Parameter: Cmax of TAF, Tenofovir (TFV), ATV, and Elvitegravir (EVG) [ Time Frame: Week 4 to Week 12 ]
    Cmax is defined as the maximum concentration of drug.
  • Part 2: PK Parameter: AUCtau of TFV, ATV, and EVG [ Time Frame: Week 4 to Week 12 ]
    AUCtau is defined as concentration of drug over time.
  • Part 2: PK Parameter: Ctau of TFV, ATV, and EVG [ Time Frame: Week 4 to Week 12 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.
  • 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 ]
Not Provided
Not Provided
 
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
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

Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which approximately 10 participants will be enrolled to receive open-label tenofovir alafenamide (TAF) in addition to their current failing antiretroviral (ARV) regimen. This cohort will then be followed by a randomized, double-blind, cohort of approximately 90 participants 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.

Not Provided
Interventional
Phase 3
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: 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
  • HIV
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Drug: TAF
    25 mg tablet administered orally once daily with food
  • 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.
  • 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.
    Interventions:
    • Drug: E/C/F/TAF
    • Drug: ATV
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
55
June 2017
May 9, 2016   (Final data collection date for primary outcome measure)

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
  • Screening or historical genotype report showing either 1 to 3 thymidine-analogue mutations (TAMs) and/or K65R, as well as M184V/I
  • 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.

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Dominican Republic,   Russian Federation,   Thailand,   Uganda,   United States
Australia,   Canada,   Germany,   Poland,   United Kingdom
 
NCT01967940
GS-US-292-0117
2013-002830-19 ( EudraCT Number )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Not Provided
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Gilead Study Director Gilead Sciences
Gilead Sciences
May 2017

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