This is a Phase 2, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, and efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1-3-selective tyrosine kinase inhibitor, in children 3 to 11 years of age with Achondroplasia (ACH) who previously participated in the PROPEL study (Protocol QBGJ398-001) for at least 6 months. The study includes dose escalation with extended treatment, and dose expansion. The study also includes a PK Substudy to fully characterize the pharmacokinetics of infigratinib in children with ACH.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Initial cohort dose of infigratinib at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
UCSF Benioff Children's Hospital
Oakland, California, United States
Nemours Alfred I. Dupont Hospital for Children
Wilmington, Delaware, United States
Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation
Time frame: Up to 18 months
Change from baseline in annualized height velocity
Time frame: Up to 18 months
PK parameters of infigratinib (Cmax- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (Clast- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (Tmax- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (AUC24- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (T1/2- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (AUCinf- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (CL/F- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (Vz/F- PK substudy only)
Time frame: 21 days
PK parameters of infigratinib (Racc- PK substudy only)
Time frame: 21 days
Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability
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Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Johns Hopkins School of Medicine
Baltimore, Maryland, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Murdoch Children's Hospital
Parkville, Victoria, Australia
Stollery Children's Hospital
Edmonton, Alberta, Canada
Hopital Femme Mere Enfant
Lyon, France
Hopital Necker-Enfants Malades
Paris, France
Hopital des Enfants
Toulouse, France
...and 9 more locations
Time frame: Up to 18 months
Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to ACH and non-ACH tables
Time frame: Up to 18 months
Absolute and change from baseline in weight (kg)
Time frame: Up to 18 months
Absolute and change from baseline in sitting height (cm)
Time frame: Up to 18 months
Absolute and change from baseline in head circumference (cm)
Time frame: Up to 18 months
Absolute and change from baseline in upper and lower arm length (cm)
Time frame: Up to 18 months
Absolute and change from baseline in thigh length (cm)
Time frame: Up to 18 months
Absolute and change from baseline in knee height (cm)
Time frame: Up to 18 months
Absolute and change from baseline in arm span (cm)
Time frame: Up to 18 months
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)
Time frame: Up to 18 months
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)
Time frame: Up to 18 months
Changes in pharmacodynamic parameters by assessing collagen X marker
Time frame: Up to 18 months