Evaluation of Long-term Safety and Tolerability of Sotatercept (MK-7962) in Patients with Pulmonary Arterial Hypertension on Standard Care

The primary objective of this study is to evaluate the long-term **safety** and tolerability of **sotatercept** administered using a weight-banded dosing approach in participants with **Pulmonary Arterial Hypertension (PAH)** who are on standard of care. This is clinically relevant as it aims to ensure that the therapeutic regimen is safe for long-term use, which is crucial for managing a chronic condition like PAH. The study does not list any secondary objectives.

The clinical trial involves a total of **145 participants** diagnosed with **Pulmonary Arterial Hypertension (PAH)**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on their completion of the treatment period of the previous study MK-7962-024 (LIGHTRAY) without discontinuation of the study intervention and their ability to safely enroll in the current study MK-7962-031 (LIGHTRAY EXTENSION). The trial does not include a vulnerable population. Participants have not started treatment with commercially available sotatercept. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is designed to evaluate the long-term safety and tolerability of **sotatercept** administered using a weight-banded approach in participants with **pulmonary arterial hypertension** (PAH) who are on standard care. This is a Phase 4, open-label extension study, which follows a non-randomized, single-arm design. The trial is expected to commence recruitment on May 15, 2025, and is estimated to conclude by September 30, 2027. Participants will receive **sotatercept** as a **solution for injection** via the subcutaneous route, with a maximum daily dose of 90 mg and a total dose not exceeding 5200 mg over a treatment period of up to 30 days.

The study involves several key visits, beginning with the inclusion (screening) visit, where eligibility is confirmed based on criteria such as completion of the treatment period of the previous study (MK-7962-024) and the absence of prior treatment with commercially available **sotatercept**. Following the screening, participants will undergo regular follow-up visits to monitor safety and tolerability, with the primary endpoints being the number of participants experiencing adverse events (AEs) and those discontinuing the study due to AEs. The end-of-study visit will mark the conclusion of the participant's involvement, which is anticipated to last for the duration of the treatment period, up to 30 days.

Participants may be subject to early termination from the study if they experience significant adverse events or if they commence treatment with commercially available **sotatercept**. The trial is not categorized as low intervention, and it is conducted under the orphan drug designation, reflecting its focus on a rare condition. The study aims to provide valuable insights into the long-term use of **sotatercept** in managing PAH, contributing to the understanding of its safety profile and therapeutic potential.

The clinical trial involves the administration of **Sotatercept**, a **biological** product, as the experimental medication. Sotatercept is provided in the form of a **solution for injection** and is administered via the **subcutaneous** route. The dosing regimen follows a weight-banded approach, with a maximum daily dose of 90 mg and a total maximum dose of 5200 mg over a treatment period of up to 30 days. The product is not formulated for pediatric use and is designated as an orphan drug under the designation number EU/3/20/2369. The product is identified by the sponsor product code MK-7962 and is manufactured by Merck & Co. Inc. The active substance, Sotatercept, is a protein of other origin, and the product is co-packaged with medical devices intended for sterile fluid path provision, reconstitution of lyophilized medicine, and preparation of the skin prior to injection.

In addition to the experimental treatment, participants in the study will continue to receive **standard-of-care therapy** for **pulmonary arterial hypertension (PAH)**. This standard therapy is not specified in the trial documentation but is expected to be consistent with current clinical guidelines for the management of PAH. The trial is designed to evaluate the long-term safety and tolerability of Sotatercept when administered alongside standard-of-care treatments. Compliance with the dosing schedule and administration procedures will be monitored throughout the study to ensure adherence to the protocol.

The efficacy of **sotatercept** in the clinical trial will be assessed primarily through the evaluation of safety and tolerability in participants with Pulmonary Arterial Hypertension (PAH) who are on standard care. The primary endpoints for efficacy assessment include 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 will provide insights into the long-term safety profile of **sotatercept** when administered using a weight-banded dosing approach.