Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01968551
First received: September 26, 2013
Last updated: September 24, 2014
Last verified: September 2014
  Purpose

This open-label, multicenter study is to evaluate switching from optimized antiretroviral (ARV) regimens to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus darunavir (DRV) relative to current antiretroviral regimens (ARV), and to evaluate the efficacy, safety, and tolerability of the E/C/F/TAF STR+DRV in virologically suppressed, HIV-1 positive participants.

  • Cohort 1: 20 participants will receive E/C/F/TAF STR+DRV once daily. At Week 4, safety and efficacy data from the 20 subjects in Cohort 1 will be reviewed prior to randomizing additional subjects in Cohort 2. Cohort 1 subjects will continue treatment with E/C/F/TAF plus DRV for a total of 48 weeks.
  • Cohort 2: 150 participants will be randomized in a 2:1 ratio to receive E/C/F/TAF STR+DRV once daily, or remain on their current, pre-existing, ARV regimen.

Condition Intervention Phase
HIV-1
HIV Infections
Acquired Immunodeficiency Syndrome
Drug: E/C/F/TAF
Drug: DRV
Drug: Pre-existing ARV regimen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of subjects in each treatment arm in Cohort 2 with HIV-1 RNA < 50 copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects in each treatment arm in Cohort 2 with HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: September 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Participants will receive E/C/F/TAF STR+DRV once daily with food for 48 weeks.
Drug: E/C/F/TAF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily
Drug: DRV
Darunavir (DRV) 800 mg administered orally once daily
Experimental: Cohort 2, Treatment Arm 1
Participants will be randomized to receive E/C/F/TAF STR+DRV once daily with food for 48 weeks.
Drug: E/C/F/TAF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily
Drug: DRV
Darunavir (DRV) 800 mg administered orally once daily
Active Comparator: Cohort 2, Treatment Arm 2
Participants will be randomized to continue on their current, pre-existing ARV regimen for 48 weeks.
Drug: Pre-existing ARV regimen
Participants will take their preexisting ARV regimen as prescribed.

  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
  • History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents
  • Plasma HIV-1 RNA levels < 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV 1 RNA levels (< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.
  • Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily)or available documentation of genotype/phenotype within 12 months prior to current regimen which must shows no evidence of resistance to integrase inhibitors
  • Normal ECG
  • Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft Gault formula for creatinine clearance
  • Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm3; platelets ≥ 50,000/mm3; hemoglobin ≥ 8.5 g/dL)
  • Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
  • A female subject is eligible to enter the study if it is confirmed that she is:

    • Not pregnant or nursing
    • Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or 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.
    • Female subjects 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.
  • Male subjects 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.
  • Male subjects 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 (except CD4 cell count and/or percentage criteria)
  • Hepatitis B surface antigen (HBsAg) positive
  • Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study.
  • Must not have Q151M, T69ins, or > 3 TAMS present on documented historic genotype report
  • Subjects experiencing decompensated cirrhosis
  • Females who are breastfeeding
  • Positive serum pregnancy test
  • Have an implanted defibrillator or pacemaker
  • Current alcohol or substance use that may interfere with subject study compliance
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 visit
  • Any other clinical condition or prior therapy that would make the subject 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
  • Subjects receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or subjects with any known allergies to the study drugs.
  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: NCT01968551

  Show 84 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Moupali Das, MD, MPH Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01968551     History of Changes
Other Study ID Numbers: GS-US-292-0119
Study First Received: September 26, 2013
Last Updated: September 24, 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
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Darunavir
Emtricitabine
Tenofovir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014