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: July 7, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
HIV
HIV Infections
Acquired Immunodeficiency Syndrome
Drug: TAF
Drug: Placebo to match TAF
Drug: E/C/F/TAF
Drug: Pre-existing ARV regimen
Drug: ATV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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


Estimated Enrollment: 100
Study Start Date: August 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: TAF
Tenofovir alafenamide (TAF) 25 mg tablet 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: 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

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 (Subjects with positive 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01967940

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Southern California Men's Medical Group
Los Angeles, California, United States, 90069
United States, Florida
Therafirst Medical Center
Fort Lauderdale, Florida, United States, 33308
Midway Immunology and Research center
Fort Pierce, Florida, United States, 34982
Valuhealthmd/ Idocf
Orlando, Florida, United States, 32806
Triple O Research Institute, P.A.
West Palm Beach, Florida, United States, 33401
Rowan Tree Medical, P.A.
Wilton Manors, Florida, United States, 33305
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Missouri
Central West Clinical Reseach
St. Louis, Missouri, United States, 63108
United States, New Jersey
Saint Michaels Medical Center
Newark, New Jersey, United States, 07102
South Jersey Infectious Disease
Somers Point, New Jersey, United States, 08244
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27705
Duke University Health System
Durham, North Carolina, United States, 27710
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Penn Presbyterian Medical Center
Philadelphia, Pennsylvania, United States, 19104
Philadelphia FIGHT
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
North Texas Infectious Diseases Consultants, P.A.
Dallas, Texas, United States, 75246
Trinity Health & Welllness Center
Dallas, Texas, United States, 75208
Gordon E. Crofoot MD PA
Houston, Texas, United States, 77098
Australia, New South Wales
Holdsworth House Medical Practice
Darlinghurst, New South Wales, Australia, 2010
Dominican Republic
Salvador B Gautier Hospital - Infectious Diseases Department
Santo Domingo, Dominican Republic, 10514
Instituto Dominicano de Estudio Virologicos - IDEV
Santo Domingo, Dominican Republic
Russian Federation
Regional state budget health agency Krasnoyarsk Regional Center for Prevention and Control of AIDS
Krasnoyarsk, Russian Federation, 660049
Federal Center for Prevention and Control of AIDS, Moscow
Moscow, Russian Federation, 105275
Orel Regional Center for Prevention and Control of AIDS and Infectious Diseases
Moscow, Russian Federation, 129110
Regional Center For Prevention and Treatment of AIDS and Infectious Diseases, Nizhniy Novgorod
Nizhniy Novgorod, Russian Federation, 603950
Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg
Saint Petersburg, Russian Federation, 190020
Center For Prevention and Treatment of AIDS and Infectious Diseases, Saint Petersburg
St. Petersburg, Russian Federation, 190103
Thailand
Ramathibodi Hospital, Mahidol University
Bangkok, Thailand, 10400
Siriraj Hospital Department of Preventive and Social Medicine, Faculty of Medicine
Bangkok, Thailand, 10700
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
Bangkok, Thailand, 10330
Chiang Mai University
Chiang Mai, Thailand, 50200
Khon Kaen University
Khon Kaen, Thailand, 40002
Uganda
Joint Clinical Research Centre
Kampala, Uganda
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Hal Martin, MD, MPH Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01967940     History of Changes
Other Study ID Numbers: GS-US-292-0117, 2013-002830-19
Study First Received: October 18, 2013
Last Updated: July 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV-1
HIV
Treatment-Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Emtricitabine
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015