ESPE Abstracts (2021) 94 P2-332

1Children’s Health Ireland at Temple Street, Dublin, Ireland; 2Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom; 3University of Arkansas for Medical Sciences, Little Rock, USA; 4Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 5Johannes Kepler University Linz, Linz, Austria; 6University of Missouri-Columbia, Columbia, USA; 7Ascendis Pharma, Inc., Palo Alto, USA; 8Ascendis Pharma, A/S, Hellerup, Denmark; 9Murdoch Children’s Research Institute and University of Melbourne, Melbourne, Australia

Achondroplasia (ACH) is the most common form of dwarfism, occurring in 1: 20,000 births. ACH is caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that interfere with endochondral ossification. Clinically significant morbidities are frequent in ACH; however, there are currently no approved therapies that target the underlying pathobiology. C-type natriuretic peptide (CNP) is an attractive target as it has the potential to inhibit the overactive FGFR3 signalling pathways. TransCon CNP is an investigational once-weekly prodrug of CNP in development for children with ACH. In the Phase 1 trial, doses up to 150 μg CNP/kg of TransCon CNP were well-tolerated in healthy adult male volunteers, with no clinically significant trends observed in laboratory assessments, vital sign measurements, ECG parameters, or physical examination findings. Conducted at approximately 20 sites, the primary objective of the phase 2 ACcomplisH trial is to evaluate the safety and efficacy of once-weekly TransCon CNP compared to placebo at 12 months in prepubertal children, aged 2-10 years old, with ACH. Following screening and genetic confirmation of clinical ACH, approximately 60 subjects will be randomized to receive either TransCon CNP or placebo and will remain within the dose cohort for 52 weeks of treatment. TransCon CNP will be dosed 6 to 100 μg CNP/kg/week across 4 cohorts, with an optional 5th cohort at a higher dose. After completing 52 weeks of their assigned cohort dose, participants who fulfill the rollover criteria can continue into the 104 week open-label extension. The primary efficacy endpoint will evaluate annualized height velocity at 52 weeks treatment of TransCon CNP or placebo. Key secondary endpoints will examine change from baseline in upper to lower body segment ratio at Week 52. The trial will also examine other endpoints associated with weekly TransCon CNP, including safety, pharmacokinetics (PK), and quality of life (QoL). CNP is targeted specifically to the underlying pathology of ACH through inhibition of FGFR3 signaling. TransCon CNP is designed to provide sustained exposure of CNP over one week. This ongoing Phase 2 ACcomplisH Trial is designed to assess the safety, efficacy, QoL, and PK of TransCon CNP by weekly administration compared to placebo. Multisystem Endocrine Disorders

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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