Back to resultsSafety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults (BETAF-RED)
Primary Purpose
HIV Infections
Status
Active
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Biktarvy 50 mg/200 mg/25 mg film-coated tablets
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria: Stable and asymptomatic HIV-infected adults (≥18 years) on BETAF once daily for at least the previous 6 months. Plasma HIV-1 RNA less than 50 copies/mL for at least the previous 6 months. CD4 cell counts greater than 350 cells/mL at the time of consideration for the study. Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods. Patients agreed to participate. Exclusion Criteria: Prior virological failure to any antiretroviral regimen or documented. Any diagnosis of psychiatric illness. Alcohol abuse or illicit drug consumption (based on their past medical history and specific questions at the time of recruitment). Patients co-infected with HIV and active hepatitis B or C virus. Any other condition at the doctor's discretion that did not allow ensuring a correct adherence.
Sites / Locations
- Hospital Clinic i Provincial Barcelona
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Arm Label
BETAF OD arm
BETAF 3W arm
BETAF 2W arm
BETAF 1W arm
Arm Description
one tablet taken orally once daily
one tablet taken orally 3 days per week : Mondays, Wednesdays, and Fridays
one tablet taken orally 2 days per week : Mondays, and Thursdays
one tablet taken orally 1 days per week : Mondays
Outcomes
Primary Outcome Measures
Viral efficacy of the reduction of BETAF regimen dose per week at 12 weeks.
standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL
Viral efficacy of the reduction of BETAF regimen dose per week at 48 weeks.
standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL
Secondary Outcome Measures
Virological efficacy assessed by Standard plasma viral load
-Standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL)
Virological efficacy assessed by Blips (VL ≥50 copies/mL followed)
-Blips (VL ≥50 copies/mL followed)
Virological efficacy assessed by Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)
-Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)
Virological efficacy assessed by Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)
-Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)
Virological efficacy assessed by HIV-1 reservoir (total and integrated DNA (copies/106 PBMC)) in CD4 cells
- HIV-1 reservoir (total and integrated DNA) in CD4 cells
Virological efficacy assessed by ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance
In case of virological failure, ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance
Immunological safety assessed by CD4 and CD8 cells
-CD4 and CD8 (cells/mL) will be combined to report CD4/CD8 ratio.
Immunological safety 2 assessed by hsCRP, IL-6 and adiponectin levels
-Inflammation (hsCRP, IL-6, adiponectin) (µg/mL), IL-6 (pg/mL), adiponectin (µg/mL) levels
Immunological safety assessed by sCD14 and CD163 as a Immune activation markers
- sCD14(ng/l ) and CD163 (ng/l) plasma levels
Subclinical toxicity assessed by BMI index
- Weight and body mass index (BMI)(kg/m2) changes
Body composition assessed by DEXA scan
-Body composition (g/cm) (fat, fat-free mass, and bone by DEXA)
Impact on sleep quality assessed by Pittsburg Sleep Quality
- Impact on sleep quality will be evaluated througth Pittsburg Sleep Quality (visual analog score)questionaire at 0 and 48 weeks
Quality of life questionnaire assessed by EuroQol Group EQ-5D™ questionnaire
- Impact on quality of life will be evaluated througth EuroQol Group EQ-5D™ (Units on a Scale)
Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) assessed by Plasma levels of bictegravir, emtricitabine and tenofovir
- Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)
Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim)
Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)
Full Information
NCT ID
NCT05602506
First Posted
October 19, 2022
Last Updated
September 18, 2023
Sponsor
Fundacion Clinic per a la Recerca Biomédica
1. Study Identification
Unique Protocol Identification Number
NCT05602506
Brief Title
Safety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults
Acronym
BETAF-RED
Official Title
Safety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 15, 2022 (Actual)
Primary Completion Date
November 15, 2024 (Anticipated)
Study Completion Date
July 3, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fundacion Clinic per a la Recerca Biomédica
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase IV, unicentric, open, pilot, randomized, controlled trial to evaluate Bictegravir/FTC/TAF. The study will be developed at a single clinical care centre:Hospital Clínic de Barcelona, Barcelona, Spain. The aim of this study is to assess the feasibility of dose redutions of Bictegravir/FTC/TAF in virologically suppressed HIV-infected adults on BETAF once daily. The reduction of drug exposure will have a significant positive impact on parameters reflecting potential toxicities associated with bictegravir or tenofovir.
Detailed Description
The Primary objectives are:
To assess viral efficacy of the reductions of BETAF regimen dose at 12 weeks (on-treatment and intent-to-treat populations).
To asess viral efficacy of the reduction of BETAF regimen dose at 48 weeks (on-treatment and intent-to-treat populations).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BETAF OD arm
Arm Type
Active Comparator
Arm Description
one tablet taken orally once daily
Arm Title
BETAF 3W arm
Arm Type
Experimental
Arm Description
one tablet taken orally 3 days per week : Mondays, Wednesdays, and Fridays
Arm Title
BETAF 2W arm
Arm Type
Experimental
Arm Description
one tablet taken orally 2 days per week : Mondays, and Thursdays
Arm Title
BETAF 1W arm
Arm Type
Experimental
Arm Description
one tablet taken orally 1 days per week : Mondays
Intervention Type
Drug
Intervention Name(s)
Biktarvy 50 mg/200 mg/25 mg film-coated tablets
Intervention Description
The duration of the study treatment will be 48 weeks.
Primary Outcome Measure Information:
Title
Viral efficacy of the reduction of BETAF regimen dose per week at 12 weeks.
Description
standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL
Time Frame
at 12 weeks
Title
Viral efficacy of the reduction of BETAF regimen dose per week at 48 weeks.
Description
standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL
Time Frame
at 48 weeks.
Secondary Outcome Measure Information:
Title
Virological efficacy assessed by Standard plasma viral load
Description
-Standard plasma viral load, lower limit of detection HIV RNA 50 copies/mL)
Time Frame
at 4, 24, and 36 weeks.
Title
Virological efficacy assessed by Blips (VL ≥50 copies/mL followed)
Description
-Blips (VL ≥50 copies/mL followed)
Time Frame
at 0, 4, 12, 24, 36, and 48 weeks
Title
Virological efficacy assessed by Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)
Description
-Target not detected with standard plasma viral load (VL ≥ HIV RNA 50 copies/mL)
Time Frame
at 0, 4, 12, 24, 36, and 48 weeks
Title
Virological efficacy assessed by Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)
Description
-Ultrasensitive plasma viral load (lower limit of detection 5 copies/mL)
Time Frame
at 0, 12, and 48 weeks.
Title
Virological efficacy assessed by HIV-1 reservoir (total and integrated DNA (copies/106 PBMC)) in CD4 cells
Description
- HIV-1 reservoir (total and integrated DNA) in CD4 cells
Time Frame
at 0, 12, and 48 weeks.
Title
Virological efficacy assessed by ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance
Description
In case of virological failure, ultra-deep sequencing of plasma and intracellular viral load to detect genotypic resistance
Time Frame
at 0, 4, 12, 24, 36 and 48 weeks
Title
Immunological safety assessed by CD4 and CD8 cells
Description
-CD4 and CD8 (cells/mL) will be combined to report CD4/CD8 ratio.
Time Frame
at 0, 12 and 48 weeks
Title
Immunological safety 2 assessed by hsCRP, IL-6 and adiponectin levels
Description
-Inflammation (hsCRP, IL-6, adiponectin) (µg/mL), IL-6 (pg/mL), adiponectin (µg/mL) levels
Time Frame
at 0, 12 and 48 weeks
Title
Immunological safety assessed by sCD14 and CD163 as a Immune activation markers
Description
- sCD14(ng/l ) and CD163 (ng/l) plasma levels
Time Frame
at 0, 12 and 48 weeks
Title
Subclinical toxicity assessed by BMI index
Description
- Weight and body mass index (BMI)(kg/m2) changes
Time Frame
at 4, 12, 24, 36, and 48
Title
Body composition assessed by DEXA scan
Description
-Body composition (g/cm) (fat, fat-free mass, and bone by DEXA)
Time Frame
at 0 and 48 weeks
Title
Impact on sleep quality assessed by Pittsburg Sleep Quality
Description
- Impact on sleep quality will be evaluated througth Pittsburg Sleep Quality (visual analog score)questionaire at 0 and 48 weeks
Time Frame
at 0 and 48 weeks
Title
Quality of life questionnaire assessed by EuroQol Group EQ-5D™ questionnaire
Description
- Impact on quality of life will be evaluated througth EuroQol Group EQ-5D™ (Units on a Scale)
Time Frame
at 0 and 4,12,24,36, 48 weeks
Title
Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) assessed by Plasma levels of bictegravir, emtricitabine and tenofovir
Description
- Minimum plasma concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)
Time Frame
at 0, 12, and 48 weeks
Title
Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim)
Description
Minimum intracellular concentration of bictegravir, emtricitabine and tenofovir (Cmim) (μg/L)
Time Frame
at 0, 12, and 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Stable and asymptomatic HIV-infected adults (≥18 years) on BETAF once daily for at least the previous 6 months.
Plasma HIV-1 RNA less than 50 copies/mL for at least the previous 6 months.
CD4 cell counts greater than 350 cells/mL at the time of consideration for the study.
Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods.
Patients agreed to participate.
Exclusion Criteria:
Prior virological failure to any antiretroviral regimen or documented.
Any diagnosis of psychiatric illness.
Alcohol abuse or illicit drug consumption (based on their past medical history and specific questions at the time of recruitment).
Patients co-infected with HIV and active hepatitis B or C virus.
Any other condition at the doctor's discretion that did not allow ensuring a correct adherence.
Facility Information:
Facility Name
Hospital Clinic i Provincial Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety, Tolerability, and Efficacy of a Dose Reduction Strategy Based on Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-infected Adults
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