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 August 2014 by Gilead Sciences
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01967940
First received: October 18, 2013
Last updated: August 6, 2014
Last verified: August 2014
  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: September 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: October 2014 (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) 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
  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

Contacts
Contact: Anne Thomas Anne.Thomas@gilead.com

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact    205-975-7925      
United States, California
Pacific Oaks Medical Group Recruiting
Beverly Hills, California, United States, 90211
Contact    310-652-2562      
OASIS Clinic/Charles Drew University Recruiting
Los Angeles, California, United States, 90059
Contact    310-668-5033      
Anthony Mills MD Inc Recruiting
Los Angeles, California, United States, 90069
Contact    310-550-2271      
Peter J. Ruane, MD Recruiting
Los Angeles, California, United States, 90036
Contact    323-954-1072      
United States, Colorado
Kaiser Permanente Colorado Recruiting
Denver, Colorado, United States, 80205
Contact    303-861-3133      
United States, Connecticut
World Health Clinicians dba Circle Care Center Not yet recruiting
Norwalk, Connecticut, United States, 06850
Contact    203-852-9525      
United States, District of Columbia
Dupont Circle Physician's Group Recruiting
Washington, District of Columbia, United States, 20009
Contact    202-745-0201      
United States, Florida
Therafirst Medical Center Recruiting
Fort Lauderdale, Florida, United States, 33308
Contact    954-564-4222      
Midway Immunology and Research center Recruiting
Fort Pierce, Florida, United States, 34982
Contact    772-464-9746      
Valuhealthmd/ Idocf Recruiting
Orlando, Florida, United States, 32806
Contact    407-246-1946      
St. Joseph's Comprehensive Research Institute Recruiting
Tampa, Florida, United States, 33614
Contact    813-870-4760      
Hillsborough County Health Department Recruiting
Tampa, Florida, United States, 33602
Contact    813-307-8067      
Triple O Research Institute, P.A. Recruiting
West Palm Beach, Florida, United States, 33401
Contact    561-855-7871      
Rowan Tree Medical, P.A. Recruiting
Wilton Manors, Florida, United States, 33305
Contact    954-533-5382      
United States, Georgia
Kaiser Foundation Health Plan of Georgia, Inc. Withdrawn
Atlanta, Georgia, United States, 30305
AIDS Research Consortium of Atlanta Recruiting
Atlanta, Georgia, United States, 30312
Contact    404-876-2317      
United States, Illinois
Howard Brown Health Center Recruiting
Chicago, Illinois, United States, 60613
Contact    773-388-8792      
The Ruth M. Rothstein CORE Center Not yet recruiting
Chicago, Illinois, United States, 60612
Contact    312-572-4543      
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact    502-852-8842      
United States, Massachusetts
The Research Institute Recruiting
Springfield, Massachusetts, United States, 01105
Contact    413-747-5566      
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact    313-916-3451      
United States, Minnesota
Abbott Northwestern Hospital Recruiting
Minneapolis, Minnesota, United States, 55404
Contact    612-325-8520      
United States, Missouri
The Kansas City Free Health Clinice/KC Care Clinic Recruiting
Kansas City, Missouri, United States, 64111
Contact    816-777-2759      
Southampton Healthcare, Inc. Recruiting
Saint Louis, Missouri, United States, 63139
Contact    314-647-2200      
Central West Clinical Reseach Recruiting
St. Louis, Missouri, United States, 63108
Contact    314-652-0100      
United States, New Jersey
New Jersey Medical School Not yet recruiting
Newark, New Jersey, United States, 07013
Contact    973-972-1268      
Saint Michaels Medical Center Recruiting
Newark, New Jersey, United States, 07102
Contact    973-877-2735      
South Jersey Infectious Disease Recruiting
Somers Point, New Jersey, United States, 08244
Contact    609-927-6662      
Garden State Infectious Disease Associates, PA Withdrawn
Voorhees, New Jersey, United States, 08043
United States, New York
Beth Israel Medical Center Recruiting
New York, New York, United States, 10003
Contact    212-420-4005      
University of Rochester Not yet recruiting
Rochester, New York, United States, 14642
Contact    585-276-5903      
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27705
Contact    919-843-8761      
Carolinas Medical Center--Myer's Park Recruiting
Charlotte, North Carolina, United States, 28207
Contact    704-446-1638      
Duke University Health System Recruiting
Durham, North Carolina, United States, 27710
Contact    919-668-0166      
East Carolina University The Brody School of Medicine, Infectious Diseases Recruiting
Greenville, North Carolina, United States, 27858
Contact    252-744-5700      
Rosedale Infectious Diseases Recruiting
Huntersville, North Carolina, United States, 28078
Contact    704-948-8582      
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact    336-716-8978      
United States, Pennsylvania
Penn Presbyterian Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    215-662-8217      
Philadelphia FIGHT Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact    215-985-4448      
United States, Texas
North Texas Infectious Diseases Consultants, P.A. Recruiting
Dallas, Texas, United States, 75246
Contact    214-276-5618      
Trinity Health & Welllness Center Recruiting
Dallas, Texas, United States, 75208
Contact    972-807-7370      
Gordon E. Crofoot MD PA Recruiting
Houston, Texas, United States, 77098
Contact    713-526-0005      
Therapeutic Concepts, PA Recruiting
Houston, Texas, United States, 77004
Contact    713-526-9821      
United States, Washington
Peter Shalit, MD Recruiting
Seattle, Washington, United States, 98104
Contact    206-624-1441      
Canada, British Columbia
Vancouver ID Research and Care Centre Society Recruiting
Vancouver, British Columbia, Canada, V5Z 2C7
Contact    604-642-6429      
Canada, Quebec
Clinique Médicale du Quartier Latin Not yet recruiting
Montreal, Quebec, Canada, H2L 5B1
Contact    514-285-5500      
Clinique OPUS Inc Recruiting
Montreal, Quebec, Canada, H3A 1T1
Contact    514-707-7389      
Research Institute of the MUHC Recruiting
Montreal, Quebec, Canada, H2X 2P4
Contact    514-934-1934      
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: August 6, 2014
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
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Tenofovir
Tenofovir disoproxil
Atazanavir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014