Evaluation of Budigalimab and ABBV-382 Efficacy, Safety, and Pharmacokinetics in HIV Patients on Stable Antiretroviral Therapy Undergoing Analytical Treatment Interruption

The primary objective of this Phase 2, multicenter, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy**, safety, tolerability, and pharmacokinetics (PK) of Budigalimab and/or ABBV-382 compared to placebo in individuals living with **HIV infection** who are on stable antiretroviral therapy (ART) and undergoing analytical treatment interruption (ATI). This evaluation is clinically relevant as it aims to assess the potential of these investigational agents to improve treatment outcomes and manage HIV infection more effectively during periods of ART interruption.

The clinical trial involves a total of **104 participants** diagnosed with **HIV infection**. The study population includes both male and female participants aged between 18 and 70 years, all of whom are in general good health. Participants have been on antiretroviral therapy (ART) for at least 12 months prior to screening and on their current ART regimen for at least 8 weeks prior to screening. The selection criteria required participants to have a negative HIV-2 antibody at screening, plasma HIV-1 RNA levels below the lower limit of quantification at screening and for at least 12 months prior, and a CD4+ T cell count of 500 cells/μL or higher at screening, with no known evidence of a CD4+ T cell count below 500 cells/μL in the last 12 months prior to screening. The trial includes a vulnerable population, and lifestyle factors such as diet and physical activity were not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics of Budigalimab and/or ABBV-382 in individuals living with **HIV infection** who are on stable antiretroviral therapy (ART) and undergoing analytical treatment interruption (ATI). The trial is set to commence recruitment on March 1, 2024, and is expected to conclude by December 31, 2026. Participants will be randomly assigned to receive either Budigalimab, ABBV-382, or a placebo, with the primary endpoint being viral control, defined as a viral load of less than 1000 copies/mL at Week 24 without restarting ART.

The study will involve several key visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, health status, and ART history. Participants must be between 18-70 years old, in good health, and have been on ART for at least 12 months prior to screening. They must also have a plasma HIV-1 RNA level below the lower limit of quantification and a CD4+ T cell count of at least 500 cells/μL. Follow-up visits will be scheduled to monitor the participants' health, viral load, and any adverse events. The end-of-study visit will occur after the completion of the treatment period, which is up to 8 weeks for ABBV-382 and 6 weeks for Budigalimab.

Participant involvement is expected to last for the duration of the treatment period plus any additional follow-up required to assess the primary and secondary endpoints. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial aims to provide valuable insights into the potential benefits of Budigalimab and ABBV-382 in managing HIV infection during ART interruption.

The clinical trial involves the administration of **Budigalimab**, a humanized, recombinant IgG1 monoclonal antibody (mAb). Budigalimab is provided in a **solution for injection/infusion** form. The administration routes include **intravenous (IV)** or **subcutaneous (SC)**. The maximum treatment period for Budigalimab is six weeks, with dosing schedules determined by the study protocol. Participant compliance will be monitored through regular assessments and documentation of administration.

Another experimental medication used in the trial is **ABBV-382**, which is also a humanized, recombinant IgG1 mAb with FcγR binding ability. ABBV-382 is available as a **solution for injection/infusion** and is administered via **infusion**. The maximum treatment period for ABBV-382 is eight weeks. Dosing schedules and participant compliance will be monitored similarly to Budigalimab, ensuring adherence to the study protocol.

The trial includes a **placebo** for Budigalimab, consisting of 0.9% sodium chloride or diluent. This placebo is used to maintain the double-blind nature of the study. The pharmaceutical form and administration route for the placebo are not specified, but it is assumed to mimic the administration of Budigalimab to ensure blinding.

Additionally, a **placebo** for ABBV-382 is utilized in the study. This placebo is designed to resemble the ABBV-382 solution for infusion, ensuring that participants and investigators remain blinded to the treatment assignments. The specific pharmaceutical form and administration route for this placebo are not detailed, but it is expected to align with the administration of ABBV-382.

Efficacy in this clinical trial will be assessed through a series of predefined primary and secondary endpoints. The primary endpoint is the achievement of **viral control** defined as a viral load of less than 1000 copies/mL at Week 24 without the need to restart antiretroviral therapy (ART). Secondary endpoints include the measurement of peak viral load at the point of rebound prior to the re-initiation of ART and the time to the first viral rebound to 1000 copies/mL or more during the ART interruption period.

These efficacy parameters will be collected and analyzed at specific timepoints throughout the trial, with a particular focus on Week 24 for the primary endpoint. The trial is designed to evaluate the efficacy of Budigalimab and/or ABBV-382 in individuals living with HIV who are on stable ART and undergoing an analytical treatment interruption. The study will employ a randomized, double-blind, placebo-controlled design to ensure the reliability and validity of the efficacy assessments.