(mo)BETTA Trial in Transwomen for Optimization of ART

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and tolerability of a new HIV medication, bictegravir plus emtricitabine plus tenofovir alafenamide (B/FTC/TAF, 3 HIV medications combined into one pill) in HIV-infected transgender women (TW).

Official Title
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Bictegravir, Emtricitabine and Tenofovir Alafenamide in Transwomen for Optimization of ART: The (mo)BETTA Trial

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: B/FTC/TAF
* Drug: Current ART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self-identified transgender woman (TW) HIV infection Undetectable HIV viral load (HIV-1 RNA <50 copies/mL) at screening and for >/=24 weeks prior to entry. Current HIV treatment with FTC plus TDF or TAF and a 3rd agent. No changes in ART in the 12 weeks prior to screening. Current female hormone therapy use. Ability and willingness of subject to provide informed consent. Exclusion Criteria: Current or planned use of prohibited medications (Phenobarbital, Phenytoin, Carbamazepine, Oxcarbazepine, Rifampin, Rifapentine, St. John's Wort, Echinacea, Dofetilide, Cisapride, Atazanavir) Change or initiation of lipid- and/or glucose-lowering therapy in the 12 weeks prior to entry, or planned need for such therapy during the study period. Current use of androgen therapy. Intent to significantly modify diet or exercise habits, or to enroll in a weight loss intervention during the study period. Anticipated need to initiate or change doses of medications with anti-inflammatory properties within the study period. Screening laboratory values as follows: (ANC <500 cells/mm^3; Hemoglobin <10 gm/dL; Cr Cl <30 mL/min (estimated by CKD-Epi equation); AST or ALT >3x ULN) Evidence of resistance to any component of the current ART regimen (genotypic or phenotypic) Current use of bictegravir in another investigational setting Current use of other investigational agents that the participant could not receive unchanged, if needed, throughout the study period (unless approved by the study team) Any condition that the study investigator believes would make the candidate unsuitable for participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Switch ART<br>Switch from current antiretroviral therapy (ART) to bictegravir + tenofovir alafenamide + emtricitabine (B/FTC/TAF) for 48 weeks | Drug: B/FTC/TAF<br>* B/FTC/TAF is bictegravir + tenofovir alafenamide + emtricitabine in one pill (single tablet regimen)<br>|
| Active Comparator: Continue Current ART<br>Continue current antiretroviral therapy (ART) therapy (which is emtricitabine plus tenofovir disoproxil fumarate or tenofovir alafenamide plus 3rd agent) for 48 weeks. | Drug: Current ART<br>* Current ART is emtricitabine plus tenofovir disoproxil fumarate or tenofovir alafenamide plus 3rd agent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Maintaining Undetectable HIV-1 RNA | Number of participants who maintain <50 copies/mL HIV-1 RNA for 48 weeks | 48 weeks | 
| Frequency of Adverse Events | Number of participants who discontinue study drug due to study-drug related adverse events (AEs, includes >/= Grade 3 lab or clinical events) | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fat Mass, Total | Fat mass, total, as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Fat Mass, Total | Fat mass, total, as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Fat Mass, Trunk | Fat mass, trunk, as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Fat Mass, Trunk | Fat mass, trunk, as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Fat Mass, Limbs | Fat mass, limbs, as measured by Dual-energy X-ray absorptiometry (DXA) | baseline | 
| Fat Mass, Limbs | Fat mass, limbs, as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Percentage of Fat Mass (Total) | Percentage of Fat mass (total) as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Percentage of Fat Mass (Total) | Percentage of Fat mass (total) as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Percentage of Fat Mass (Trunk) | Percentage of Fat mass (trunk) as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Percentage of Fat Mass (Trunk) | Percentage of Fat mass (trunk) as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Percentage of Fat Mass (Limbs) | Percentage of Fat mass (limbs) as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Percentage of Fat Mass (Limbs) | Percentage of Fat mass (limbs) as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Lean Mass (Total) | lean mass (total) as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Lean Mass (Limb) | lean mass (limb) as measured by Dual-energy X-ray absorptiometry (DXA) | Baseline | 
| Lean Mass (Total) | lean mass (total) as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Lean Mass (Limb) | lean mass (limb) as measured by Dual-energy X-ray absorptiometry (DXA) | 48 weeks | 
| Hepatic Fat Content | The controlled attenuation parameter (CAP) indicates quantity of fat in the liver (that is, hepatic fat content). CAP is assessed by performing transient elastography (TE) using a FibroScan device, which uses ultrasound. The CAP score is measured in decibels per meter (dB/m). CAP score ranges from 100 dB/m to 400 dB/m, and a higher score indicates greater hepatic fat content. | Baseline | 
| Hepatic Fat Content | The controlled attenuation parameter (CAP) indicates quantity of fat in the liver (that is, hepatic fat content). CAP is assessed by performing transient elastography (TE) using a FibroScan device, which uses ultrasound. The CAP score is measured in decibels per meter (dB/m). CAP score ranges from 100 dB/m to 400 dB/m, and a higher score indicates greater hepatic fat content. | 48 weeks | 
| Total Cholesterol | Total cholesterol level | Baseline | 
| Total Cholesterol | Total cholesterol level | 48 weeks | 
| High-density Lipoprotein (HDL) Cholesterol Level |  | Baseline | 
| High-density Lipoprotein (HDL) Cholesterol Level |  | 48 weeks | 
| Triglycerides | Triglyceride level | Baseline | 
| Triglycerides | Triglyceride level | 48 weeks | 
| Low-density Lipoprotein (LDL) Cholesterol Level |  | Baseline | 
| Low-density Lipoprotein (LDL) Cholesterol Level |  | 48 weeks | 
| Fasting Glucose Level | Fasting Glucose level | Baseline | 
| Fasting Glucose Level | Fasting Glucose level | 48 weeks | 
| Insulin Resistance | The Homeostatic Assessment Model of Insulin Resistance (HOMA-IR) is an index used to determine if insulin resistance is present. HOMA-IR is calculated as ([(fasting insulin in mU/L) x (glucose in mmol/L)]/22.5). Higher HOMA-IR values indicate greater insulin resistance. The threshold HOMA-IR value that indicates insulin resistance differs among different populations, but a common clinical cutoff is 2.6 (in other words, a HOMA-IR value of 2.6 or above is commonly interpreted to indicate insulin resistance). | Baseline | 
| Insulin Resistance | The Homeostatic Assessment Model of Insulin Resistance (HOMA-IR) is an index used to determine if insulin resistance is present. HOMA-IR is calculated as ([(fasting insulin in mU/L) x (glucose in mmol/L)]/22.5). Higher HOMA-IR values indicate greater insulin resistance. The threshold HOMA-IR value that indicates insulin resistance differs among different populations, but a common clinical cutoff is 2.6 (in other words, a HOMA-IR value of 2.6 or above is commonly interpreted to indicate insulin resistance). | 48 weeks | 
| Oxidized Low-density Lipoprotein (LDL) Level | Oxidized Low-density Lipoprotein (LDL) levels are assessed by testing blood | Baseline | 
| Oxidized Low-density Lipoprotein (LDL) Level | Oxidized Low-density Lipoprotein (LDL) levels are assessed by testing blood | 48 weeks | 
| Hepatic Fibrosis as Indicated by Liver Stiffness Measurement | Fibrosis (that is, scarring of the liver) results in liver stiffness, and liver stiffness can be measured by liver elastography using a FibroScan device, which uses ultrasound. The liver stiffness measurement ranges from 2 kPa to 75 kPa, with a higher score indicating greater liver scarring and stiffness | Baseline | 
| Hepatic Fibrosis as Indicated by Liver Stiffness Measurement | Fibrosis (that is, scarring of the liver) results in liver stiffness, and liver stiffness can be measured by liver elastography using a FibroScan device, which uses ultrasound. The liver stiffness measurement ranges from 2 kPa to 75 kPa, with a higher score indicating greater liver scarring and stiffness | 48 weeks | 
| Aspartate Aminotransferase (AST) Level |  | Baseline | 
| Aspartate Aminotransferase (AST) Level |  | 48 weeks | 
| Alanine Transaminase (ALT) Level |  | Baseline | 
| Alanine Transaminase (ALT) Level |  | 48 weeks | 
| Estimated Glomerular Filtration Rate (CKD- Epi Equations) | glomerular filtration rate (GFR) level | Baseline | 
| Estimated Glomerular Filtration Rate (CKD- Epi Equations) | glomerular filtration rate (GFR) level | 48 weeks | 
| Level of Adiponectin | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Adiponectin | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Endothelin-1 | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Endothelin-1 | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Extracellular Newly Identified Receptor for Advanced Glycation End-products Binding Protein (EN-RAGE) | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Extracellular Newly Identified Receptor for Advanced Glycation End-products Binding Protein (EN-RAGE) | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Tumor Necrosis Factor Receptor I (TNFRI) | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Tumor Necrosis Factor Receptor I (TNFRI) | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Tumor Necrosis Factor Receptor II (TNFRII) | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Tumor Necrosis Factor Receptor II (TNFRII) | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Insulin | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Insulin | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of D-dimer | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of D-dimer | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Tissue Factor | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Tissue Factor | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Soluble CD14 (sCD14) | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Soluble CD14 (sCD14) | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Level of Plasminogen Activator Inhibitor (PAI-1) | Inflammatory and metabolic biomarkers level | Baseline | 
| Level of Plasminogen Activator Inhibitor (PAI-1) | Inflammatory and metabolic biomarkers level | 48 weeks | 
| Bone Mineral Density (BMD), Femur Total Mean | BMD as measured by dual-energy x-ray absorptiometry (DXA) | Baseline | 
| Bone Mineral Density (BMD), Femur Total Mean | BMD as measured by dual-energy x-ray absorptiometry (DXA) | 48 weeks | 
| Bone Mineral Density (BMD), AP-spine L1-L4 | BMD as measured by dual-energy x-ray absorptiometry (DXA) | Baseline | 
| Bone Mineral Density (BMD), AP-spine L1-L4 | BMD as measured by dual-energy x-ray absorptiometry (DXA) | 48 weeks | 
| T-Score AP-spine L1-L4 | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | Baseline | 
| T-Score AP-spine L1-L4 | Bone mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | 48 weeks | 
| T-Score Total Body | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | Baseline | 
| T-Score Total Body | Bone mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | 48 weeks | 
| Bone Mineral Density (BMD), Total Body | BMD as measured by dual-energy x-ray absorptiometry (DXA) | Baseline | 
| T-Score Femur Total Mean | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | Baseline | 
| T-Score Femur Total Mean | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | 48 weeks | 
| T-Score Femur Neck Mean | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | Baseline | 
| T-Score Femur Neck Mean | Bone Mineral Density T-score as measured by dual-energy x-ray absorptiometry (DXA) A T-score between +1 and -1 is considered normal or healthy. A T-score between -1 and -2.5 indicates osteopenia. A T-score of -2.5 or lower indicates osteoporosis | 48 weeks | 
| Bone Mineral Density (BMD), Femur Neck Mean | BMD as measured by dual-energy x-ray absorptiometry (DXA) | 48 weeks | 
| Bone Mineral Density (BMD), Femur Neck Mean | BMD as measured by dual-energy x-ray absorptiometry (DXA) | Baseline | 
| Bone Mineral Density (BMD), Total Body | BMD as measured by dual-energy x-ray absorptiometry (DXA) | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transgender women, Bictegravir