Endocrine Abstracts

JOINT315

Objectives: The primary objective of the OraGrowtH Phase 3 study is to evaluate the efficacy of daily oral LUM-201 (1. 6 mg/kg) in improving growth velocity over 12 months in prepubertal children with GHD. LUM-201, an oral growth hormone secretagogue (GHS), acts on the GHS receptor 1a in the pituitary and hypothalamus to stimulate GH release. Clinical evidence suggests that LUM-201 increases GH pulse amplitude, resulting in increased insulin-like growth factor 1 (IGF-1) and growth. The FDA has acknowledged that, due to LUM-201’s unique mechanism of action, its efficacy can be compared to placebo or injectable GH, which delivers GH concentrations about five times greater than physiological levels. 1. 6 mg/kg/day dose was selected based on prior pediatric studies. This study seeks to clinically validate the predictive enrichment marker (PEM) classification, which identifies patients who respond to LUM-201, by assessing changes in growth velocity, IGF-1 SDS, and height SDS over 12 months.

Methods: The OraGrowtH Phase 3 Trial, (global, multicenter, 12-month, randomized, double-blind, placebo-controlled) will enroll treatment-naïve, prepubertal children with GHD who test positive for PEM at screening. A positive PEM result is defined as a baseline IGF-1 concentration > 30. 0 ng/mL and a peak serum GH concentration ≥ 5. 0 ng/mL following a single dose of LUM-201. 150 subjects will be randomized in a 2:1 ratio to receive either daily LUM-201 or placebo (identical capsules) for 12 months. Subjects will attend clinic visits every three months until Month 12. At 12 months subjects will be eligible for an extension trial receiving LUM-201 for up to three years. During the trial, measurements such as height, body weight, and vital signs will be tracked. Safety assessments will include laboratory tests, ECGs, and pharmacokinetic and pharmacodynamic data. Bone age will be evaluated with standard X-rays at screening and Month 12 visits. Adverse events and the use of concomitant medications will be monitored and documented at each visit.

Results: The detailed study design will be presented at the meeting.

Conclusions: LUM-201 represents a novel investigational treatment option for patients with GHD. By stimulating endogenous GH release via the GH-releasing hormone pathway and reducing somatostatin activity, LUM-201 preserves the physiological feedback loop, distinguishing it from exogenous GH injections. The OraGrowtH Phase 3 trial aims to further evaluate LUM-201’s efficacy and safety as an oral treatment for GHD.