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 currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01967940
First received: October 18, 2013
Last updated: September 15, 2014
Last verified: September 2014

October 18, 2013
September 15, 2014
September 2013
October 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01967940 on ClinicalTrials.gov Archive Site
  • Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 10 (Part 1) [ Time Frame: Day 10 ] [ Designated as safety issue: No ]
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Percentage of participants with plasma HIV-1 RNA < 400 copies/mL [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HIV-1 RNA (log10 copies/mL) [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count (cells/µL) and percentage [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Safety of E/C/F/TAF STR plus ATV 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 ] [ Designated as safety issue: No ]
    Safety data will be summarized.
  • Plasma pharmacokinetics (PK) parameter of TAF as measured by AUClast, Clast, and Cmax and PK parameter of tenofovir, ATV, and elvitegravir as measured by AUCtau, Ctau, and Cmax [ Time Frame: Week 4 to Week 12 ] [ Designated as safety issue: No ]
    • AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration
    • Clast is defined as the last observable concentration of drug
    • Cmax is defined as the maximum observed concentration of drug in plasma
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • 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 ] [ Designated as safety issue: No ]
  • Percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Percentage of participants with plasma HIV-1 RNA < 400 copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count (cells/µL) and percentage at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
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 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 to compare the addition of TAF or placebo-to-match TAF in HIV-1 positive adults who are failing their current ARV regimen. This randomized cohort will consist of approximately 90 participants.

In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo-to-match TAF 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 single-tablet regimen (E/C/F/TAF 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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV
  • HIV Infections
  • Acquired Immunodeficiency Syndrome
  • Drug: TAF
    Tenofovir alafenamide (TAF) 25 mg tablet administered orally once daily with food
  • Drug: Placebo to match TAF
    Placebo tablets to match TAF administered orally once daily with food
  • Drug: E/C/F/TAF
    Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regiment (STR) administered orally once daily with food
  • Drug: Pre-existing ARV regimen
    Participants will continue taking their pre-existing ARV regimen as prescribed in Part 1.
  • Drug: ATV
    ATV 300 mg tablet administered orally once daily.
  • Experimental: TAF followed by E/C/F/TAF plus ATV
    Participants will be randomized to receive TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period. After this period, participants with a > 0.5 log10 decline in HIV-1 RNA will then receive E/C/F/TAF plus ATV for 48 weeks in Part 2.
    Interventions:
    • Drug: TAF
    • Drug: E/C/F/TAF
    • Drug: Pre-existing ARV regimen
    • Drug: ATV
  • Experimental: Placebo followed by E/C/F/TAF plus ATV
    Participants will receive placebo to match TAF plus their pre-existing ARV regimen for 10 days in Part 1, followed by a 14-day washout period, and then receive E/C/F/TAF plus ATV for 48 weeks in Part 2 regardless of HIV-1 RNA value.
    Interventions:
    • Drug: Placebo to match TAF
    • Drug: E/C/F/TAF
    • Drug: Pre-existing ARV regimen
    • Drug: ATV
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
February 2015
October 2014   (final data collection date for primary outcome measure)

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) or K65R, as well as M184V, and at least one primary NNRTI and/or PI mutation
  • 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.

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
  • 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
Both
18 Years and older
No
Contact: Anne Thomas Anne.Thomas@gilead.com
United States,   Canada
 
NCT01967940
GS-US-292-0117, 2013-002830-19
Yes
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Hal Martin, MD, MPH Gilead Sciences
Gilead Sciences
September 2014

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