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Efficacy, Safety & Tolerability of Switching EFV/TDF/FTC to BIC/FTC/TAF in Virologically Suppressed Adults With HIV-1

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03502005
Recruitment Status : Completed
First Posted : April 18, 2018
Last Update Posted : January 22, 2020
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Midland Research Group, Inc.

Brief Summary:
This study evaluates the efficacy, safety and tolerability of switching from the older, established single tablet regimen of ATRIPLA® (EFV/FTC/TDF) to a new single tablet regimen of BIKTARVY® (BIC/FTC/TAF), in HIV-1 infected adult subjects who are virologically suppressed (HIV-1 RNA<50 copies/mL).

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: bictegravir/emtricitabine/tenofovir alafenamide Phase 4

Detailed Description:

Therapeutic dosage of the tenofovir disoproxil fumarate (TDF) component of ATRIPLA® requires plasma concentrations of the drug that are associated with nephrotoxicity and decreased bone mineral density. Tenofovir alafenamide fumarate (TAF) has a unique metabolism that results in higher intracellular levels of the active phosphorylated moiety tenofovir-diphosphate. Compared with TDF, the therapeutic dosage of TAF reduces tenofovir plasma concentrations by over 90%. This reduction in plasma concentration results in decreased renal and bone risks. TAF has the potential to improve on the efficacy and safety profile of TDF.

Efavirenz, another component of ATRIPLA® is widely associated with neuropsychiatric side-effects, including sleep disturbances, depression, and anxiety. Switching from Efavirenz to an integrase inhibitor is associated with improvements in mood.

Bictegravir (BIC) is a novel, once daily integrase inhibitor. It has been shown to have potent antiviral activity, a favorable pharmacokinetic profile, good tolerability and an improved resistance profile when compared to previous integrase inhibitors. In a phase 2 trial investigating previously untreated people with HIV, bictegravir plus emtricitabine and tenofovir alafenamide (BIKTARVY®) vs dolutegravir, plus emtricitabine and tenofovir alafenamide both showed high efficacy up to 24 weeks and both regimens were well tolerated.

Additionally, switching HAART experienced patients to BIKTARVY® has been shown to be non-inferior to continuation of regimens containing Atazanavir or Darunavir, when they were given with either lamivudine/abacavir or FTC/TDF.

The Investigators plan to evaluate in a real world setting the efficacy, safety and tolerability of switching from the older, established single tablet regimen of ATRIPLA® (EFV/FTC/TDF) to a new single tablet regimen of BIKTARVY® (BIC/FTC/TAF).

Within the limitations of a real-world study, Investigators have attempted to replicate the protocol of Gilead Science's Phase 3 study evaluating a switch to BIC/FTC/TAF from dolutegravir plus either FTC/TAF or FTC/TDF14. This will have the potential benefit of comparing different regimen switches as well as potentially adding robustness to the body of data regarding BIC/FTC/TAF.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Prospective 48 week single cohort study to evaluate the efficacy and safety of switching from ATRIPLA to BIKTARVY® in HIV-1 infected adult subjects who are virologically suppressed (HIV-1 RNA < 50 copies/mL).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: "Efficacy, Safety, and Tolerability of Switching EFV/TDF/FTC to BIC/FTC/TAF in Virologically Suppressed Adults With HIV-1 Infection."
Actual Study Start Date : March 1, 2018
Actual Primary Completion Date : December 30, 2019
Actual Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: BIKTARVY®
initiation of single pill once daily bictegravir/emtricitabine/tenofovir alafenamide from prior efavirenz/emtricitabine/tenofovir DF
Drug: bictegravir/emtricitabine/tenofovir alafenamide
Discontinue ATRIPLA® and initiate BIKTARVY®
Other Name: BIKTARVY® (BIC/FTC/TAF)




Primary Outcome Measures :
  1. assess proportion of patients who develop increase in HIV-1 RNA viral load of ≥ 50 copies/mL [ Time Frame: 24 weeks ]
    by week 24


Secondary Outcome Measures :
  1. assess stability of kidney function by serial measuring of serum creatinine mg/dL [ Time Frame: 48 weeks ]
    weeks 24 and 48

  2. Assess effect on restoration of immune markers by serial measurement of CD4+ cells [ Time Frame: 48 weeks ]
    weeks 24 and 48

  3. assess effect on lipid cardiovascular risk factors by serial measurement of triglycerides and HDL/LDL cholesterol [ Time Frame: 48 weeks ]
    weeks 24 and 48

  4. assess proportion of patients who continue to have HIV-1 RNA measured <50 copies/mL [ Time Frame: 48 weeks ]
    weeks 24 and 48

  5. Assess patient reported outcomes by two validated patient questionnaires Philadelphia Sleep Quality Index and HIV Symptom Index [ Time Frame: 48 weeks ]
    by week 48

  6. assess patient weight variations from baseline [ Time Frame: 48 weeks ]
    weeks 24 and 48



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV positive
  • On a stable antiretroviral regimen consisting of ATRIPLA® for at least the 6 consecutive months preceding Screening Visit.
  • Plasma HIV-1 RNA concentrations at undetectable levels for at least 6 consecutive months prior to the screening visit and have HIV RNA< 50 copies/mL at the Screening Visit.
  • Estimated GFR ≥30mL/min according to the Cockcroft-Gault formula for creatinine clearance.
  • Hepatic transaminases (AST and ALT) ≤5x upper limit of normal (ULN)
  • Total bilirubin ≤1.5 mg/dL, or normal direct bilirubin.
  • Adequate hematologic function (hemoglobin ≥ 8.5g/dL; platelets ≥ 50,000/mm3; absolute neutrophil count ≥1,000/mm3)
  • Female subjects of reproductive potential using a reliable and consistent method of birth control for at least three months prior to study dosing. Male subjects should use condoms when engaging in intercourse of reproductive potential.
  • The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.

Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within 30 days prior to screening.
  • Individuals with decompensated cirrhosis. (i.e. ascites, encephalopathy, etc.)
  • Pregnancy
  • A 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, noninvasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible but must not have received any systemic therapy for KS within 30 days prior to baseline.
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline.
  • Life expectancy < 1 year.
  • Subject participation in any clinical trial without prior approval from the Investigator.
  • Concomitant use of disallowed agents from Table 2
  • Participation in any other investigation study 30 days prior to enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03502005


Locations
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United States, Florida
Midland Research Group, Inc
Oakland Park, Florida, United States, 33334
Sponsors and Collaborators
Midland Research Group, Inc.
Gilead Sciences
Investigators
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Principal Investigator: Noah Lee, DO Midland Research Group, Inc.
  Study Documents (Full-Text)

Documents provided by Midland Research Group, Inc.:
Informed Consent Form  [PDF] November 1, 2018

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Responsible Party: Midland Research Group, Inc.
ClinicalTrials.gov Identifier: NCT03502005    
Other Study ID Numbers: IN-US-380-4543
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: CROI 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Tenofovir
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents