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.
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.
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.
Parallel
Infigratinib is provided as a single dose of minitablets for oral administration
Drug* The initial cohort dose of infigratinib will begin at the protocol-specified starting dose, with subsequent cohort escalation based on protocol specific criteria. * The dose and number of minitablets will be calculated based on individual participant age and weight.
Infigratinib is provided as sprinkle capsules for daily oral administration
Drug* The cohort dose of infigratinib will be the dose identified in the Single Ascending Dose portion for the age group. * The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months.
Infigratinib or placebo comparator is provided as sprinkle capsules for daily oral administration
Drug* The cohort dose of infigratinib or placebo will be the dose confirmed in the Phase 2 portion for the age group. * The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months.
Infigratinib is provided as sprinkle capsules for daily oral administration
Drug* The dose of infigratinib will be the dose confirmed in the Phase 2 portion and used in the Phase 2b portion for the age group. * The dose and number of sprinkle capsules/day will be calculated based on individual participant age and weight. Doses will be adjusted based on age and weight changes approximately every 3 months for the first year and every 6 months thereafter.
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Treatment groupsSee each treatment group below.
Single Ascending Dose Portion: Identify the dose of infigratinib to be used in each age cohort of the Phase 2 potion of the study (by assessing safety and PK of infigratinib and its active metabolites)
Phase 2 Portion: Confirm the doses to be used in each age cohort in the Phase 2b portion of the study (by assessing safety and PK of infigratinib and its active metabolites).
Phase 2b Portion: Evaluate the safety and efficacy of infigratinib in infants and children < 3 years old with ACH (by assessing AE's & SAE's)
Extension Portion: Evaluate the safety and efficacy of infigratinib in participants who completed the Phase 2 or Phase 2b portion of the study until they have reached 3 years old (+6 months) (by assessing AE's and SAE's)
Phase 2: Evaluate the safety of oral daily doses of infigratinib (by assessing AEs and SAEs)
Phase 2: Evaluate changes in indicators of growth (by assessing change from BL in body length z-score at Week 52 in relation to ACH tables)
Phase 2: Evaluate changes in indicators of body proportions (by assessing change from BL to Week 52 in upper-to-lower body segment ratio and head circumference/body length ratio)
Phase 2: Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Infant and Toddler Quality of Life Inventory [ITQoL] tool)
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