Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Midland Research Group, Inc.

Collaborator
Gilead Sciences

Information provided by (Responsible Party)
Midland Research Group, Inc.
ClinicalTrials.gov Identifier
NCT03502005

First received: March 14, 2018
Last updated: January 17, 2020
Last Verified: August 2019
History of Changes
Purpose

Purpose

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 Intervention Phase
Human Immunodeficiency Virus

Drug : bictegravir/emtricitabine/tenofovir alafenamide
Phase 4

Study Type: Interventional
Study Design: 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."

Further study details as provided by Midland Research Group, Inc.:

Primary Outcome Measures

  • 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:
  • assess stability of kidney function by serial measuring of serum creatinine mg/dL [ Time Frame: 48 weeks ]
    weeks 24 and 48
  • Assess effect on restoration of immune markers by serial measurement of CD4+ cells [ Time Frame: 48 weeks ]
    weeks 24 and 48
  • assess effect on lipid cardiovascular risk factors by serial measurement of triglycerides and HDL/LDL cholesterol [ Time Frame: 48 weeks ]
    weeks 24 and 48
  • assess proportion of patients who continue to have HIV-1 RNA measured <50 copies/mL [ Time Frame: 48 weeks ]
    weeks 24 and 48
  • Assess patient reported outcomes by two validated patient questionnaires Philadelphia Sleep Quality Index and HIV Symptom Index [ Time Frame: 48 weeks ]
    by week 48
  • assess patient weight variations from baseline [ Time Frame: 48 weeks ]
    weeks 24 and 48

Enrollment: 100
Study Start Date: March 1, 2018
Study Completion Date: December 30, 2019
Primary Completion Date: December 30, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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)

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.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
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.

contacts and locations

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: NCT03502005

Locations

United States, Florida
Midland Research Group, Inc
Oakland Park, Florida, United States, 33334

Sponsors and Collaborators

Midland Research Group, Inc.
Gilead Sciences

Investigators

Principal Investigator: Noah Lee, DO Midland Research Group, Inc.
More Information

More Information


Responsible Party: Midland Research Group, Inc.  
ClinicalTrials.gov Identifier: NCT03502005   History of Changes  
Other Study ID Numbers: IN-US-380-4543  
Study First Received: March 14, 2018  
Last Updated: January 17, 2020  
Individual Participant Data    
Plan to Share IPD: Undecided  

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:
Acquired Immunodeficiency Syndrome
HIV Infections
Tenofovir
Emtricitabine

ClinicalTrials.gov processed this data on May 24, 2020
This information is provided by ClinicalTrials.gov.