Evaluation of Bictegravir/Lenacapavir Versus Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Patients

The primary objective of this study is to evaluate the **efficacy** of switching to a fixed-dose combination of bictegravir/lenacapavir (BIC/LEN) tablets compared to continuing on the current regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in individuals with **HIV-1 infection** who are virologically suppressed. This evaluation is clinically relevant as it may offer insights into alternative treatment options that could enhance patient outcomes and potentially improve adherence by simplifying the treatment regimen.

Secondary objectives include:

• Evaluating the efficacy of the study drugs for the two treatment groups in virologically suppressed individuals with HIV-1, as determined by viral load suppression rate and CD4 cell count.
• Assessing the long-term efficacy of BIC/LEN in participants from Treatment Group 1, based on viral load suppression rate and CD4 cell count.
• Evaluating the safety and tolerability of the study drugs for the two treatment groups.
• Assessing the long-term safety and tolerability of BIC/LEN in participants from Treatment Group 1.

The clinical trial involves a total of **426 participants** diagnosed with **HIV-1 infection**. The study population includes both male and female subjects, aged 18 years and older, who are virologically suppressed and have been receiving a regimen of bictegravir/emtricitabine/tenofovir alafenamide for at least six months prior to screening. Participants were selected based on their current health status, specifically their plasma HIV-1 RNA levels being consistently below 50 copies/mL, and the absence of documented or suspected resistance to the medications involved in the study. The trial also considers lifestyle factors such as the use of protocol-specified methods of contraception for participants assigned female at birth and of childbearing potential. The study population includes individuals from vulnerable groups, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographics. The selection criteria emphasize maintaining a stable health status, with an estimated glomerular filtration rate greater than 30 mL/min, ensuring participants are in a suitable condition to undergo the trial. The sponsor has not provided additional information regarding specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of switching to a fixed-dose combination of **bictegravir** and **lenacapavir** versus continuing on a regimen of **bictegravir**, **emtricitabine**, and **tenofovir alafenamide** in virologically suppressed individuals with **HIV-1 infection**. This is a Phase 3, double-blind, multicenter, randomized, active-controlled study. The trial is expected to commence recruitment on July 1, 2024, and conclude by December 28, 2029. Participants will be randomly assigned to either the test group receiving bictegravir/lenacapavir or the control group continuing with their current therapy. The trial will be conducted over a period of 96 weeks, with primary and secondary endpoints assessed at Weeks 48 and 96, respectively.

Study visits are structured to ensure comprehensive monitoring and data collection. The inclusion visit, or screening, will confirm eligibility based on criteria such as age, current treatment regimen, and virological suppression status. Participants must have an **HIV-1 RNA** level of less than 50 copies/mL at screening and no documented resistance to the study drugs. Follow-up visits will occur at regular intervals to monitor **HIV-1 RNA** levels, **CD4 cell count**, and any treatment-emergent adverse events. The end-of-study visit will finalize data collection and assess the long-term efficacy and safety of the treatment regimens.

Participant involvement is expected to last up to 96 weeks, with conditions for early termination including significant adverse events or non-compliance with the study protocol. The primary endpoint is the proportion of participants with **HIV-1 RNA** levels of 50 copies/mL or more at Week 48, as determined by the US FDA-defined snapshot algorithm. Secondary endpoints include the proportion of participants with **HIV-1 RNA** levels below 50 copies/mL, changes in **CD4 cell count**, and the incidence of treatment-emergent adverse events. The trial aims to provide valuable insights into the comparative efficacy of the two treatment regimens in maintaining virological suppression in individuals with **HIV-1 infection**.

The clinical trial involves the administration of **Biktarvy** 50 mg/200 mg/25 mg film-coated tablets, which contain the active substances **emtricitabine**, **tenofovir alafenamide**, and **bictegravir**. These tablets are administered orally once daily. The maximum treatment period for this medication is 48 weeks, with a maximum total dose amount of 336 units. The pharmaceutical form is a film-coated tablet, and the medication is of chemical origin. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule.

Another experimental treatment in the trial is the **Bictegravir** 75 mg/Lenacapavir 50 mg fixed-dose combination (FDC) tablets. This medication is also administered orally, with a maximum daily dose of one tablet. The treatment period for this medication extends up to 96 weeks, with a total maximum dose amount of 672 units. The active substances, **bictegravir** and **lenacapavir**, are of chemical origin, and the pharmaceutical form is a film-coated tablet. Compliance monitoring is conducted to ensure participants adhere to the prescribed dosing regimen.

The trial also includes the administration of **Sunlenca** 300 mg film-coated tablets, containing the active substance **lenacapavir**. These tablets are administered orally, with a maximum daily dose of 600 mg and a total maximum dose amount of 1200 mg over a treatment period of 2 weeks. The pharmaceutical form is a film-coated tablet, and the active substance is of chemical origin. Participant adherence to the dosing schedule is monitored throughout the trial.

In addition to the experimental treatments, the trial utilizes placebo tablets as a comparator. These placebo tablets are designed to match the appearance of the active treatments but do not contain any active pharmaceutical ingredients. The placebo is administered in a similar manner to the active treatments to maintain the double-blind nature of the study. Compliance with placebo administration is also monitored to ensure the integrity of the trial results.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints related to the treatment of **HIV-1** in virologically suppressed individuals. The primary endpoint is the proportion of participants with HIV-1 RNA levels ≥ 50 copies/mL at Week 48, as determined by the United States Food and Drug Administration (FDA)-defined snapshot algorithm. Secondary endpoints include the proportion of participants with HIV-1 RNA levels < 50 copies/mL at Week 48, change from baseline in CD4 cell count at Week 48, and the proportion of participants from Treatment Group 1 with HIV-1 RNA levels ≥ 50 copies/mL and < 50 copies/mL at Week 96. Additionally, the change from baseline in CD4 cell count at Week 96 for participants from Treatment Group 1 will be assessed, along with the proportion of participants experiencing treatment-emergent adverse events through Week 48 and Week 96.

The efficacy parameters will be measured and collected at specified timepoints, including Week 48 and Week 96, using the FDA-defined snapshot algorithm. The analysis will focus on comparing the efficacy of switching to bictegravir/lenacapavir (BIC/LEN) fixed-dose combination tablets versus continuing on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) fixed-dose combination tablets. The trial is designed to ensure rigorous assessment of the efficacy endpoints, providing valuable insights into the treatment outcomes for individuals with HIV-1.