ESPE Abstracts (2021) 94 P1-130

1Murdoch Children’s Research Institute, Melbourne, Australia; 2Hospital Vithas San José, Vitoria-Gasteiz, Spain; 3Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom; 4Hôpital des Enfants - Toulouse, Toulouse, France; 5Hospital Universitario Virgen de la Victoria, Malaga, Spain; 6Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, United Kingdom; 7NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; 8Hospital Universitario La Paz, Madrid, Spain; 9Hôpital Necker-Enfants Malades, Paris, France; 10University of Alberta - Stollery Children’s Hospital, Edmonton, Canada; 11Manchester University NHS Foundation Trust, Manchester, United Kingdom; 12Nemours/Alfred I. duPont Hospital for Children, Wilmington, USA; 13Vanderbilt University Medical Center, Nashville, USA; 14University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, USA; 15Benioff Children’s Hospital Oakland, Oakland, USA; 16Cincinnati Children’s Hospital Medical Center, Cincinnati, USA; 17QED Therapeutics, San Francisco, USA; 18Guy’s and Saint Thomas’ NHS Foundation Trust, London, United Kingdom

Background: ACH is the most common short-limbed skeletal dysplasia, affecting between 1 in 15,000 to 1 in 30,000 live births. Children and adults with ACH have disproportionate short stature, with a final height of approx. 131 cm for males and 124 cm for females. People with ACH are prone to significant co-morbidities, including obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. In some infants, narrowing of the foramen magnum may result in compression of the spinal cord with neurologic sequelae, requiring timely neurosurgical intervention. There are currently no approved therapies for the treatment of ACH in either the US or the EU, and current treatment options are non-targeted, ineffective, or painful interventions aimed at preventing or treating complications of ACH. Infigratinib is an oral FGFR1–3 inhibitor in development as a therapeutic option for ACH. The PROPEL study is a prospective, non-interventional study examining baseline growth parameters and health status in children being assessed for potential enrollment into interventional studies with infigratinib.

Methods: Children with ACH between the ages of 2.5 and 10 years are eligible for enrollment in PROPEL, and are evaluated at baseline, month 3, month 6, and every 6 months thereafter. The primary endpoint is annualized height velocity. Secondary endpoints include: change from baseline in other growth parameters (including body proportionality); analysis of bone biomarkers (e.g. bone alkaline phosphatase, collagen X fragment); and the occurrence of medical events and surgical procedures. Participants will be enrolled in the study for a minimum of 6 months up to a maximum of 2 years.

Results: A total of 75 children (64% female, mean±SD age 6.3±2.4 years) have been enrolled to date at 19 sites in Europe, Australia and North America. Their heights at study entry were within the ±2 SDs for ACH growth charts, with a mean±SD and median height percentile of 43±27 and 50 respectively, indicating that the participating children are a good representation of the population of interest. Additional demographics, baseline characteristics and medical history will be presented at the meeting.

Conclusions: The PROPEL study is underway with a planned total enrollment of 200 children with ACH. This sample size is considered enough to characterize the natural history of the condition and lead to sufficient enrollment in Phase 2 (PROPEL2) and/or Phase 3 interventional trials of infigratinib in children with ACH.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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