Long-term Safety and Efficacy Evaluation of Inhaled Seralutinib in Pulmonary Arterial Hypertension: An Open-label Extension Study

The primary objective of this study is to evaluate the long-term **safety** and tolerability of seralutinib in subjects with **Pulmonary Arterial Hypertension** (PAH). This is clinically relevant as it aims to ensure that seralutinib, when administered over an extended period, does not pose significant health risks to patients, thereby supporting its potential use as a long-term treatment option for PAH.

Secondary objectives include:

• Evaluating the long-term effect of seralutinib on exercise capacity when added to background PAH disease-specific medication. This is important for assessing whether seralutinib can improve or maintain physical function in patients.
• Evaluating the long-term effect of seralutinib on NT-proBNP levels when added to background PAH disease-specific medication. NT-proBNP is a biomarker associated with heart stress and function, and its evaluation can provide insights into the cardiovascular benefits of seralutinib.

The clinical trial involves a total of **215 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 their completion of a prior seralutinib PAH study, ensuring they have been previously exposed to the investigational product. The trial does not include a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified, but participants must demonstrate a willingness and ability to comply with scheduled visits and study procedures. Key inclusion criteria require women of childbearing potential to have a negative pregnancy test and adhere to effective contraception methods, while male participants must use condoms and refrain from sperm donation during the study period. The trial aims to evaluate the long-term safety and tolerability of seralutinib in this specific cohort.

The clinical trial is designed as a **phase 3 open-label extension study** to evaluate the long-term safety and efficacy of **seralutinib**, an inhalation powder in hard capsule form, for the treatment of **Pulmonary Arterial Hypertension (PAH)**. The trial will involve participants who have completed a prior seralutinib PAH study. The primary objective is to assess the incidence of treatment-emergent adverse events (TEAEs), while secondary endpoints include changes in the distance achieved on the six-minute walk test (6MWT) and changes in NT-proBNP levels. The trial is expected to commence recruitment on June 30, 2024, and conclude by October 31, 2028.

Participants will be involved in the study for a maximum treatment period of 52 weeks. The study will include several key visits: an inclusion (screening) visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require that participants must have completed a prior seralutinib PAH study, and women of childbearing potential must have a negative pregnancy test before enrollment. Male participants must use a condom if sexually active with a female partner of childbearing potential. Participants must provide informed consent and demonstrate willingness and ability to comply with study procedures.

Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The study is not classified as low intervention, and the investigational product, seralutinib, is administered via inhalation. The trial is sponsored by GB002, INC., and the product is designated as an orphan drug, indicating its use for a rare disease. The maximum daily dose of seralutinib is 180 mg, and the study will utilize a device with a CE mark for administration. The trial will not include a pediatric formulation, and the pharmaceutical form is specifically for adult use.

The clinical trial involves the administration of the experimental medication **seralutinib**, marketed under the product name GB002. This medication is formulated as an **inhalation powder, hard capsule** and is intended for the treatment of **pulmonary arterial hypertension (PAH)**. The active substance, seralutinib, is of chemical origin. The medication is administered via the **inhalation** route, utilizing a device that has been certified with a CE mark by IMQ S.p.A. The maximum daily dose of seralutinib is 180 mg, and the treatment period extends up to 52 weeks. The study aims to evaluate the long-term safety and tolerability of seralutinib in subjects with PAH.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, as deemed necessary by the study protocol. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed as an open-label extension study, allowing for the continuous assessment of the medication's safety and efficacy over an extended period.

The efficacy of the clinical trial evaluating the long-term safety and efficacy of **seralutinib** for the treatment of Pulmonary Arterial Hypertension (PAH) will be assessed using specific endpoints. The primary endpoint focuses on the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints include changes in the distance achieved on the six-minute walk test (6MWT), denoted as Δ6MWD, and changes in NT-proBNP levels. These parameters will be measured and collected at designated timepoints throughout the study to evaluate the therapeutic impact of seralutinib. The six-minute walk test is a validated tool commonly used to assess exercise capacity in patients with PAH, while NT-proBNP is a biomarker indicative of cardiac stress and function. The data collected will be analyzed to determine the efficacy of seralutinib in improving clinical outcomes for patients with PAH.