Evaluation of Sotatercept Pharmacokinetics and Safety in Pulmonary Arterial Hypertension Patients Undergoing Standard of Care Treatment

The primary objectives of this study are to evaluate the **steady-state systemic exposure** of sotatercept using weight-banded dosing relative to weight-based dosing following multiple dose administrations, and to assess the safety and tolerability of sotatercept over a 24-week treatment period. These objectives are clinically relevant as they aim to optimize dosing strategies for sotatercept, a treatment for **Pulmonary Arterial Hypertension (PAH)**, potentially improving therapeutic outcomes and minimizing adverse effects.

Secondary objectives include evaluating the systemic exposure of sotatercept using weight-banded dosing relative to weight-based dosing following initial dose administration. This assessment is crucial for understanding the pharmacokinetic profile of sotatercept and ensuring effective and safe dosing regimens for patients with PAH.

The clinical trial involves a total of **171 participants** diagnosed with **Pulmonary Arterial Hypertension (PAH)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific inclusion criteria, such as having a documented diagnostic Right Heart Catheterization and being classified under World Health Organization (WHO) Pulmonary Arterial Hypertension Group 1. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not specified. The trial aims to evaluate the steady-state systemic exposure of sotatercept using weight-banded dosing and assess its safety and tolerability over a 24-week treatment period.

The clinical trial is a **Phase 2**, multicenter, single-blinded, randomized study designed to evaluate the pharmacokinetics and safety of **sotatercept** (MK-7962) in participants with **pulmonary arterial hypertension** (PAH) who are on standard care. The trial aims to compare the steady-state systemic exposure of sotatercept using a weight-banded dosing approach relative to a weight-based dosing approach over a 24-week treatment period. The study will also assess the safety and tolerability of sotatercept during this time frame. The trial is expected to commence recruitment on November 18, 2024, and conclude by June 4, 2026.

Participants will be randomly assigned to receive sotatercept via subcutaneous injection, with dosing determined by either a weight-based or weight-banded method. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and pharmacokinetic parameters, and an end-of-study visit to assess overall outcomes. The primary endpoints include the steady-state average serum concentrations of sotatercept and the number of participants experiencing adverse events or discontinuing the study due to adverse events. Secondary endpoints will focus on the initial dose average serum concentrations of sotatercept.

Participant involvement is expected to last for the duration of the 24-week treatment period, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The study will adhere to rigorous methodological standards, ensuring that the trial is conducted in a controlled and scientifically valid manner. The trial's design, including its randomized and single-blinded nature, aims to minimize bias and provide reliable data on the pharmacokinetics and safety of sotatercept in the target population.

The clinical trial involves the administration of **sotatercept**, a **biological** agent, in the form of a **solution for injection**. Sotatercept, also known by its synonym ACE-011, is a protein-based therapeutic developed by Merck & Co. Inc. The pharmaceutical form is a solution intended for **subcutaneous injection**. The trial evaluates two dosing strategies: a weight-based approach and a weight-banded approach. The maximum daily dose of sotatercept is 120 mg, with a total maximum dose of 895 mg over the treatment period. The treatment period extends up to 24 weeks, during which the drug is administered at steady state to assess pharmacokinetics and safety in participants with **pulmonary arterial hypertension** (PAH) who are on standard-of-care therapy.

In addition to the experimental treatment, participants will continue to receive standard-of-care therapy for PAH, which may include medications such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs, as per the treating physician's discretion. The trial is designed to be single-blinded and randomized, ensuring that the allocation of participants to the different dosing strategies is unbiased. Compliance with the dosing regimen will be monitored throughout the study to ensure adherence to the protocol and to accurately assess the pharmacokinetic and safety outcomes of sotatercept administration.

The efficacy of **sotatercept** in the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the steady-state average serum concentrations of **sotatercept** (Cavg), the number of participants experiencing one or more adverse events (AEs), and the number of participants who discontinue the study intervention due to an AE. These endpoints are designed to evaluate both the pharmacokinetics and safety profile of **sotatercept** when administered using either a weight-based or weight-banded dosing approach in participants with Pulmonary Arterial Hypertension (PAH).

Secondary endpoints will focus on the initial dose average serum concentrations of **sotatercept** (Cavg). The trial is structured to collect and analyze these parameters over a 24-week treatment period, ensuring a comprehensive assessment of the drug's efficacy and safety. The data collection will involve regular monitoring of serum concentrations and adverse events, with the aim of determining the optimal dosing regimen for **sotatercept** in the target population. The trial's design is aligned with the main objectives of evaluating the steady-state systemic exposure and the safety and tolerability of **sotatercept** in the specified patient group.