THU164 Design Of The New InsiGHTS Trial: A Multicenter, Phase 2, Randomized, Open-label, Active Controlled Study To Investigate The Safety, Tolerability, And Efficacy Of Lonapegsomatropin In Prepubertal Individuals With Turner Syndrome

Disclosure: K.O. Klein: Advisory Board Member; Self; Abbvie, Tolmar. Consulting Fee; Self; Abbvie, Tolmar. Grant Recipient; Self; Arbor. Research Investigator; Self; Abbvie, Arbor. Speaker; Self; Abbvie. P. Backeljauw: Advisory Board Member; Self; Ascendis Pharma. Consulting Fee; Self; Novo Nordisk, Novartis Pharmaceuticals, Ascendis Pharma, BioMarin Pharmaceutical, Tolmar, Cavalry Biosciences, Ipsen. Research Investigator; Self; Novo Nordisk, Novartis Pharmaceuticals, Ipsen. Speaker; Self; Ascendis Pharma. S. Abdelrahman: Employee; Self; Ascendis Pharma. P. Lai: Employee; Self; Ascendis Pharma. M. Mao: Employee; Self; Ascendis Pharma. A. Shu: Employee; Self; Ascendis Pharma. Background: Turner syndrome (TS) is characterized by the complete or partial absence of one X chromosome. Common clinical features include skeletal disproportion (growth failure, skeletal dysplasia, and low bone mass) and premature ovarian insufficiency in addition to a range of comorbidities including increased risk of thyroid disease, heart abnormalities, and diabetes mellitus. At this time, individuals with TS are treated with daily somatropin (human growth hormone [hGH]) which is effective at promoting height gain and may improve body composition. However, daily somatropin therapy has been associated with poor adherence which may result in reduced therapeutic efficacy. Lonapegsomatropin, a once-weekly prodrug of somatropin, is currently FDA- and EMA-approved for the treatment of pediatric GHD, and safety and efficacy have been established in 3 phase 3 trials. Lonapegsomatropin uses TransCon(®) technology, which combines a parent drug transiently linked to an inert carrier to achieve sustained release of somatropin. The phase 2 New InsiGHTS trial investigates the safety, tolerability, and efficacy of once-weekly lonapegsomatropin in individuals with TS. Methods: In this phase 2, parallel arm, dose-finding study, eligible prepubertal individuals with TS (aged 1 to 10 years) from the US are planned for inclusion with the aim of randomizing 48 individuals, 1:1:1:1, to lonapegsomatropin (0.24, 0.30, 0.36 mg/kg/week) or daily somatropin (0.05 mg/kg/day [0.35 mg/kg/week], a dose consistent with treatment guidelines) and stratifying them by chronological age (<4 and ≥4 years). The primary objective is to compare once-weekly lonapegsomatropin to daily somatropin in promoting linear growth at 26 weeks. Secondary objectives include additional growth parameters, safety, adherence, and pharmacokinetic/ pharmacodynamic measures that will be assessed at specified timepoints over the 104 week treatment period. Enrolled individuals must be diagnosed with TS (confirmed by genetic testing), GH-treatment naïve, exhibit impaired growth, have bone age ≤ chronological age, and be biochemically euthyroid. Exclusion criteria include diagnosis of diabetes mellitus, history of celiac disease or known clinically significant congenital or acquired cardiac dysfunction that might interfere with growth, and treatment with growth-influencing medication, among others. Dose reductions will be allowed at any time if average insulin-like growth factor-1 standard deviation score > +2.5; and/or in case of adverse events. Conclusions: The phase 2 New InsiGHTS trial is the first time that once-weekly lonapegsomatropin will be studied in individuals with TS. New InsiGHTS will provide an opportunity to examine the impact of lonapegsomatropin in a population whose short stature is not due to GH deficiency. Presentation: Thursday, June 15, 2023