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

• ClinicalTrials.gov Identifier: NCT03502005
• Recruitment Status: Completed
• First Posted: April 18, 2018
• Last Update Posted: February 25, 2021
• Sponsor: Midland Research Group, Inc.
• Collaborator: Gilead Sciences
• Information provided by (Responsible Party): Midland Research Group, Inc.

Study Description

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.

Study Design

• 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

Arms and Interventions

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)

Outcome Measures

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

Eligibility Criteria

• 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.

Contacts and Locations

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.

  Study Documents (Full-Text)

Documents provided by Midland Research Group, Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] February 21, 2018

Informed Consent Form  [PDF] November 1, 2018

More Information

• Responsible Party: Midland Research Group, Inc.
• ClinicalTrials.gov Identifier: NCT03502005
• Other Study ID Numbers: IN-US-380-4543
• First Posted: April 18, 2018
• Last Update Posted: February 25, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: CROI 2020

• 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; Immunologic Deficiency Syndromes; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Tenofovir; Emtricitabine; Emtricitabine tenofovir alafenamide; Antiviral Agents; Anti-Infective Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents