NCT07169279 - Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH) | Crick

Eligibility

Sex: ALLMin age: 0 YearsMax age: 32 Months

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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.

Outcomes

Primary Outcomes

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)

Time frame: 2 weeks

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).

Time frame: 52 weeks

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)

Time frame: 52 weeks

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)

Time frame: 3 years and 6 months

Secondary Outcomes

Phase 2: Evaluate the safety of oral daily doses of infigratinib (by assessing AEs and SAEs)

Time frame: 52 weeks

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)

Time frame: 52 weeks

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)

Time frame: 52 weeks

Phase 2: Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Infant and Toddler Quality of Life Inventory [ITQoL] tool)

Time frame: 52 weeks

Phase 2: Milestone Development of motor skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2: Milestone Development of language skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2: Milestone Development of personal-social skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2: Skull and brain morphology (as assessed using MRI)

Time frame: 52 weeks

Phase 2: Age at closure of cranial structures (as assessed by physical examination)

Time frame: 52 weeks

Phase 2: Age at closure of fontanelles (as assessed by physical examination)

Time frame: 52 weeks

Phase 2: Incidence of surgical interventions (i.e., cervical decompression, adenotonsillectomy etc)

Time frame: 52 weeks

Phase 2: Incidence and severity of sleep apnea (as assessed by polysomnography)

Time frame: 52 weeks

Phase 2: Bone morphology (as assessed using x-rays)

Time frame: 52 weeks

Phase 2b: Evaluate the pharmacokinetic (PK) profile of infigratinib and its metabolites (by assessing the PK of infigratinib and its active metabolites)

Time frame: 52 weeks

Phase 2b: Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Infant and Toddler Quality of Life Inventory [ITQoL] tool)

Time frame: 52 weeks

Phase 2b: Evaluate the safety of oral daily doses of infigratinib (by assessing AEs and SAEs)

Time frame: 52 weeks

Phase 2b: Evaluate changes in indicators of growth (by assessing change from BL in body length z-score at Week 52 in relation to ACH tables)

Time frame: 52 weeks

Phase 2b: 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)

Time frame: 52 weeks

Phase 2b: Milestone Development of motor skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2b: Milestone development of language skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2b: Milestone development of personal-social skills (assessed with development milestone charts)

Time frame: 52 weeks

Phase 2b: Skull and brain morphology (as assessed using MRI)

Time frame: 52 weeks

Phase 2b: Age at closure of cranial structures (as assessed by physical examination)

Time frame: 52 weeks

Phase 2b: Age at closure of fontanelles (as assessed by physical examination)

Time frame: 52 weeks

Phase 2b: Incidence of surgical interventions (i.e., cervical decompression, adenotonsillectomy etc)

Time frame: 52 weeks

Phase 2b: Incidence and severity of sleep apnea (as assessed by polysomnography)

Time frame: 52 weeks

Phase 2b: Bone morphology (as assessed using x-rays)

Time frame: 52 weeks

Extension Phase: Evaluate the safety of oral daily doses of infigratinib (by assessing AEs and SAEs)