- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03502005
Efficacy, Safety & Tolerability of Switching EFV/TDF/FTC to BIC/FTC/TAF in Virologically Suppressed Adults With HIV-1
"Efficacy, Safety, and Tolerability of Switching EFV/TDF/FTC to BIC/FTC/TAF in Virologically Suppressed Adults With HIV-1 Infection."
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Florida
-
Oakland Park, Florida, United States, 33334
- Midland Research Group, Inc
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BIKTARVY®
initiation of single pill once daily bictegravir/emtricitabine/tenofovir alafenamide from prior efavirenz/emtricitabine/tenofovir DF
|
Discontinue ATRIPLA® and initiate BIKTARVY®
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
assess proportion of patients who develop increase in HIV-1 RNA viral load of ≥ 50 copies/mL
Time Frame: 24 weeks
|
by week 24
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
assess stability of kidney function by serial measuring of serum creatinine mg/dL
Time Frame: 48 weeks
|
weeks 24 and 48
|
48 weeks
|
Assess effect on restoration of immune markers by serial measurement of CD4+ cells
Time Frame: 48 weeks
|
weeks 24 and 48
|
48 weeks
|
assess effect on lipid cardiovascular risk factors by serial measurement of triglycerides and HDL/LDL cholesterol
Time Frame: 48 weeks
|
weeks 24 and 48
|
48 weeks
|
assess proportion of patients who continue to have HIV-1 RNA measured <50 copies/mL
Time Frame: 48 weeks
|
weeks 24 and 48
|
48 weeks
|
Assess patient reported outcomes by two validated patient questionnaires Philadelphia Sleep Quality Index and HIV Symptom Index
Time Frame: 48 weeks
|
by week 48
|
48 weeks
|
assess patient weight variations from baseline
Time Frame: 48 weeks
|
weeks 24 and 48
|
48 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Noah Lee, DO, Midland Research Group, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- Emtricitabine
- Emtricitabine tenofovir alafenamide
Other Study ID Numbers
- IN-US-380-4543
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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