Long-Term Safety Evaluation of Ibutamoren Mesilate in Pediatric Patients with Idiopathic Growth Hormone Deficiency

The primary objective of this study is to assess the long-term **safety** of LUM-201 administration in children with **Idiopathic Growth Hormone Deficiency** (GHD). This is clinically relevant as ensuring the safety of LUM-201 is crucial for its potential use as a therapeutic option in managing GHD, a condition characterized by insufficient production of growth hormone, leading to growth failure and other health issues in children.

Secondary objectives include:

• Assessing pharmacodynamic (PD) markers of LUM-201 treatment, which will provide insights into the drug's biological effects and mechanism of action.
• Evaluating long-term growth outcomes in response to LUM-201 treatment, which is important for understanding the efficacy of the treatment in promoting normal growth patterns in affected children.

The clinical trial involves a total of **48 participants** diagnosed with **Idiopathic Growth Hormone Deficiency**. The study population includes both male and female children, categorized under age range code 2, which typically represents a pediatric group. Participants were selected based on their successful participation in a prior pediatric LUM-201 GHD study, having met specific growth criteria after 12 months of therapy. The trial population is considered vulnerable, given the pediatric nature of the participants. Lifestyle considerations such as diet and physical activity are not specified, but subjects who are sexually active are required to use an acceptable form of contraception. The trial aims to assess the long-term safety of LUM-201 administration in this demographic.

The clinical trial is designed to assess the long-term safety of **LUM-201** administration in children with **idiopathic growth hormone deficiency**. This is a Phase 4, randomized, double-blind, controlled study. The trial is expected to run from August 1, 2023, to November 30, 2028, with a maximum treatment period of 36 months. Participants will be administered LUM-201 in tablet form, with a maximum daily dose of 1.6 mg/kg. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits every six months to monitor safety and efficacy, and an end-of-study visit to conclude participation.

Participants must have successfully completed a prior pediatric LUM-201 study and meet specific growth criteria to be eligible. The primary endpoint is the occurrence of adverse events, serious adverse events, laboratory results, and physical examination findings. Secondary endpoints include changes in growth hormone (GH) values, insulin-like growth factor 1 (IGF-1) values, insulin-like growth factor-binding protein 3 (IGFBP-3) values, height standard deviation score (HT-SDS), weight, body mass index (BMI), and bone age compared to chronological age. These parameters will be assessed every six months, with bone age evaluated annually.

Participant involvement is expected to last up to 36 months, with conditions for early termination including the occurrence of significant adverse events or failure to adhere to study protocols. The trial will ensure that all participants and their caregivers provide informed consent and assent, as applicable, and that sexually active participants use acceptable contraception methods. The study aims to provide comprehensive data on the long-term safety profile of LUM-201 in the target population.

The clinical trial involves the administration of the experimental medication **LUM-201**, which is formulated as a **TABLET**. The active substance in LUM-201 is **IBUTAMOREN MESILATE**, a chemical compound. The medication is administered orally, with a maximum daily dose of 1.6 mg/kg. The treatment period extends up to 36 months. The trial aims to assess the long-term safety of LUM-201 in children diagnosed with idiopathic growth hormone deficiency. The medication is not a pediatric formulation, and it has been designated as an orphan drug under the designation number EU/3/17/1882.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus remains solely on the administration of LUM-201. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is conducted under the sponsorship of Lumos Pharma, Inc., and the medication is authorized for use in this clinical setting.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the occurrence of adverse events (AEs), serious adverse events (SAEs), laboratory results, and physical examination findings. These parameters will be systematically collected and analyzed to evaluate the safety profile of LUM-201 in children with **idiopathic growth hormone deficiency**.

Secondary endpoints will include a range of growth and hormonal parameters measured every six months. These include actual and change over time in growth hormone (GH) values, insulin-like growth factor 1 (IGF-1) values, and insulin-like growth factor-binding protein 3 (IGFBP-3) values. Additionally, changes in height standard deviation score (HT-SDS), weight and weight SDS, body mass index (BMI) and BMI SDS will be assessed. The change in bone age compared to chronological age (BA/CA ratio) will be evaluated annually. These endpoints will provide a comprehensive assessment of the efficacy of LUM-201 in promoting growth and hormonal balance in the target population.