Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH)

Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial, Preceded by a Single Ascending Dose Portion and a Phase 2 Open-Label Portion, to Evaluate the Safety and Efficacy of Oral Infigratinib in Infants and Young Children With Achondroplasia

This is a Phase 2, multicenter, randomized, placebo-controlled study to evaluate the safety and efficacy of infigratinib in participants < 3 years old with ACH. The purposes of the SAD and Phase 2 portions are to identify and confirm the dose of infigratinib to be used in the Phase 2b portion, based on safety and PK. The purpose of the Phase 2b, placebo-controlled portion is to evaluate the safety and efficacy of infigratinib in children < 3 years old with ACH at the selected dose.

PROPEL Infant & Toddler (I&T) is a Phase 2, multicenter, randomized, placebo-controlled study that comprises 4 portions: the single ascending dose (SAD) portion (open-label), the Phase 2 portion (open-label), the Phase 2b portion (placebo-controlled), and an Extension Portion (open-label). The study will evaluate children with ACH < 3 years old being administered oral infigratinib.

Inclusion Criteria:

• Diagnosis of ACH confirmed by genetic testing. If prospective participants had prior genetic testing, the diagnosis must be confirmed by a report from a certified laboratory, documenting the specific mutation.
• Age 0 to 32 months (2 years and 8 months) at screening.
• Signed informed consent, which must be obtained from each participant's parent(s) or legal guardian.
• Parent(s)/Guardian(s) willing and able to attend all study visits and comply with all study requirements.
• Parent(s)/Guardian(s) willing and able to comply with the routine care of the study participants according to local guidance for the management of infants and young children with ACH.
• Able to swallow age-appropriate oral medication.
• In participants <1 year old, be compliant with recommended vitamin D supplementation of 5 10 μg/day or higher (or as recommended by country specific guidelines).

Exclusion Criteria:

• Participants who have hypochondroplasia or diagnosis of genetic condition other than ACH, or any clinical condition that can affect growth.
• Gestational age at birth <37 weeks and/or birth weight <2500 grams.
• Gastroesophageal reflux disease requiring prolonged treatment (>1 week) with prohibited medications.
• Evidence of cervicomedullary compression, as defined by an Achondroplasia Foramen Magnum Score (AFMS) 4, symptomatic or asymptomatic, diagnosed during MRI done at screening or a previous MRI done at any time if the participant had not undergone decompression surgery.
• History of fracture of a long bone or spine within 6 months prior to screening.
• Any other significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib and/or would require treatment with a prohibited medication (per protocol), and/or would place the participant at high risk for poor treatment compliance or for failure to complete the study.
• Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature, including (but not limited to) r-hGH, IGF-1, CNP analog, FGF ligand trap, or treatment targeting FGFR inhibition at any time.
• Regular long-term (>3 weeks; more than twice/year) treatment with supraphysiologic doses of glucocorticoid therapy (ie, >15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (for over 3 weeks within 6 months of the screening visit. NOTE: Low-dose topical, inhaled, or intranasal corticosteroids are acceptable.
• Significant abnormality in screening laboratory results,
• Allergy or hypersensitivity to any components of the study drug.