A Study to Evaluate Efficacy, Safety and Tolerability in Antiretroviral Therapy (ART)-Experienced Participants of at Least 50 Years of Age Living With Human Immunodeficiency Virus (HIV) With Virologic Suppression Who Switch to DTG/3TC FDC From BIC/FTC/TAF

Study Overview
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Brief Summary
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The study aims at evaluating the maintenance of virologic suppression of dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC) at Week 48 post-switch from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in participants living with Human Immunodeficiency Virus Type 1 (HIV-1) who are of at least 50 years of age and above.

Official Title
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A Phase 3b, Multicenter, Single-arm, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to DTG/3TC Single Tablet Regimen Administered Once Daily From a Bictegravir/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen in People Living With HIV of at Least 50 Years of Age Who Are Virologically Suppressed

Conditions
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HIV

Intervention / Treatment
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* Drug: DTG/3TC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants living with HIV-1 with documented plasma HIV-1 RNA <50 c/mL within 3 months prior to Screening. Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods [less than 30 days] where all ART was stopped due to tolerability and/or safety concerns). Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening. Participants with plasma HIV-1 RNA <50 c/mL at Screening. Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL). Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor. Exclusion Criteria: Women participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study. Participants with any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease, EXCEPT cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/cubic millimetre (mm^3) are not exclusionary. Participants with signs and symptoms which, in the opinion of the Investigator, are suggestive of active severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection within 14 days prior to enrolment. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification. Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded; Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Participants with unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment). Participants with history of liver cirrhosis with or without hepatitis viral co-infection. Participants with untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible. Participants with history or presence of allergy or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia. Participants who in the investigator's judgment, poses a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk. Participants with any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major Integrase strand transfer inhibitor (INSTI) resistance associated mutation in any available prior resistance genotype assay test result. All available historical resistance reports with HIV-1 reverse transcriptase or integrase genotypic data must be provided to ViiV after screening and before enrollment for review by ViiV Virology. Participants with any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities. Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN and bilirubin ≥1.5xULN (with greater than [>]35 percentage [%] direct bilirubin). Participant has estimated creatine clearance <30 millilitres per minute (mL/min) per 1.73 square meter (m^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants Receiving DTG/3TC FDC<br> | Drug: DTG/3TC<br>* DTG/3TC FDC will be administered once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Greater Than or Equal to (≥)50 Copies/Millilitre (c/mL) per Snapshot Algorithm at Week 48 |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Plasma HIV-1 RNA ≥50 c/mL per Snapshot Algorithm at 24 and 96 Weeks |  | Weeks 24 and 96 | 
| Number of Participants With Plasma HIV-1 RNA Less Than (<)50 c/mL per Snapshot Algorithm at 24, 48 and 96 Weeks |  | Weeks 24,48, and 96 | 
| Absolute Values for Cluster of Differentiation 4 (CD4+) Cells Count at 24, 48 and 96 Weeks |  | Weeks 24,48, and 96 | 
| Change From Baseline in CD4+ Cells Count at 24, 48 and 96 Weeks |  | Baseline (Day 1) and at Weeks 24,48, and 96 | 
| Absolute Values for CD4: Cluster of Differentiation 8 (CD8) Ratio at 24, 48 and 96 Weeks |  | Weeks 24,48, and 96 | 
| Change From Baseline in CD4:CD8 Ratio at 24, 48 and 96 Weeks |  | Baseline (Day 1) and at Weeks 24,48, and 96 | 
| Number of Participants With Disease Progression Through Weeks 24, 48 and 96 |  | Weeks 24, 48, and 96 | 
| Number of Participants who Meet Confirmed Virologic Withdrawn Criterion With Viral Resistance Over Time |  | Up to Week 96 | 
| Number of Participants With Treatment Related Non-serious Adverse Events, all Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation | A treatment related AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, and considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. | Up to Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dovato, Human Immunodeficiency Virus (HIV)-1, Dolutegravir, Lamivudine, Bictegravir, Emtricitabine, Tenofovir alafenamide, Biktarvy, Switch study, ≥ 50 years