Design of the foresiGHt Trial: A Multicenter, Randomized, Placebo- and Active-Controlled Trial to Compare Once-Weekly Lonapegsomatropin to Placebo and Daily Somatropin in Adults with Growth Hormone Deficiency (GHD)

Aleksandra Gilis-Januszewska; Maria Fleseriu; Jorgensen Jens Otto; Yuen Kevin CJ; Charlotte Hoybye; Meng Mao; Jennifer Kang; Wenjie Song; Allison Komirenko; Aimee Shu; Michael Beckert

doi:10.1530/endoabs.90.P432

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Endocrine Abstracts (2023) 90 P432 | DOI: 10.1530/endoabs.90.P432

ECE2023 Poster Presentations Pituitary and Neuroendocrinology (123 abstracts)

Design of the foresiGHt Trial: A Multicenter, Randomized, Placebo- and Active-Controlled Trial to Compare Once-Weekly Lonapegsomatropin to Placebo and Daily Somatropin in Adults with Growth Hormone Deficiency (GHD)

Aleksandra Gilis-Januszewska ¹ , Maria Fleseriu ² , Jens Otto Jørgensen ³ , Kevin CJ Yuen ⁴ , Charlotte Hoybye ⁵ , Meng Mao ⁶ , Jennifer Kang ⁶ , Wenjie Song ⁶ , Allison Komirenko ⁶ , Aimee Shu ⁶ & Michael Beckert ⁷

Err

Author affiliations

¹Jagiellonian University, Medical College, Kraków, Poland; ²Oregon Health & Science University, Portland, OR, United States; ³Aarhus University Hospital, Aarhus, Denmark; ⁴Barrow Pituitary Center, Barrow Neurological Institute and St. Joseph’s Hospital and Medical Center, University of Arizona College of Medicine, Phoenix, AZ, United States; ⁵Karolinska University Hospital, Stockholm, Sweden; ⁶Ascendis Pharma, Inc, Palo Alto, CA, United States; ⁷Ascendis Pharma A/S, Hellerup, Denmark

Background: Adult GHD results from insufficient growth hormone (GH) secretion from the anterior pituitary gland and may represent either a continuation of childhood-onset GHD or GHD acquired during adulthood. Clinically, adult GHD is associated with central adiposity, decreased lean muscle mass, increased fat mass, decreased bone mineral density, and reduced quality of life. Current standard of care consists of GH replacement via daily injections. Lonapegsomatropin (SKYTROFA; TransCon hGH), a once-weekly prodrug of somatropin approved for the treatment of pediatric GHD by the FDA and EMA, uses TransCon technology to transiently link a parent drug to an inert carrier and achieve sustained release of active, unmodified somatropin under physiologic conditions. The safety and efficacy of lonapegsomatropin have previously been evaluated in three phase 3 trials in pediatric GHD. Change in body composition in both pediatric and adult GHD reflects biologic activity of GH and clinical efficacy of GH replacement.

Methods: The primary objective of the foresiGHt trial is to evaluate the efficacy of once-weekly lonapegsomatropin compared to placebo at 38 weeks in adults with GHD. The trial has been conducted at approximately 120 sites in North America, Europe, Asia, and Oceania. Approximately 240 subjects have been randomized 1:1:1 to once-weekly lonapegsomatropin, once-weekly placebo, or daily somatropin. Subjects will be treatment-naïve or without GH therapy for at least 12 months. Subjects with well-controlled non-insulin dependent diabetes mellitus (HbA1c ≤ 7.5%) will be eligible. Following screening, the 38-week treatment period will consist of a 12-week gradual dose titration period and 26 weeks of fixed dose maintenance. Fixed dosing will be used to ensure maximal comparability across the treatment arms in the trial. Three dosing groups per arm will be established to allow for differences in age and oral estrogen intake in women. The primary endpoint is change from baseline in trunk percent fat at week 38, as measured by dual energy X-ray absorptiometry (DXA). Secondary efficacy endpoints are change from baseline in trunk fat mass and change in total body lean mass at week 38. Exploratory efficacy endpoints include total body fat mass, trunk lean mass, visceral adipose tissue, and patient-reported outcomes.

Conclusion: The ongoing global Phase 3 foresiGHt trial is designed to assess the efficacy, safety, and tolerability of lonapegsomatropin by weekly administration, compared to weekly placebo and daily hGH replacement therapy in adults with GHD.