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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infigratinib 0.016 mg/kg | Experimental | Dose Escalation: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. |
|
| Infigratinib 0.032 mg/kg | Experimental | Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. |
|
| Infigratinib 0.064 mg/kg | Experimental | Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. |
|
| Infigratinib 0.128 mg/kg | Experimental | Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infigratinib 0.016 mg/kg | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation | Up to 18 months | |
| Change from baseline in annualized height velocity | Up to 18 months | |
| PK parameters of infigratinib (Cmax- PK substudy only) | 21 days | |
| PK parameters of infigratinib (Clast- PK substudy only) | 21 days | |
| PK parameters of infigratinib (Tmax- PK substudy only) | 21 days | |
| PK parameters of infigratinib (AUC24- PK substudy only) | 21 days | |
| PK parameters of infigratinib (T1/2- PK substudy only) | 21 days | |
| PK parameters of infigratinib (AUCinf- PK substudy only) | 21 days | |
| PK parameters of infigratinib (CL/F- PK substudy only) | 21 days | |
| PK parameters of infigratinib (Vz/F- PK substudy only) | 21 days | |
| PK parameters of infigratinib (Racc- PK substudy only) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| QED Therapeutics VP, Clinical Development | QED Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital | Oakland | California | 94618 | United States | ||
| Nemours Alfred I. Dupont Hospital for Children |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39555818 | Derived | Savarirayan R, De Bergua JM, Arundel P, Salles JP, Saraff V, Delgado B, Leiva-Gea A, McDevitt H, Nicolino M, Rossi M, Salcedo M, Cormier-Daire V, Skae M, Kannu P, Phillips J 3rd, Saal H, Harmatz P, Candler T, Hill D, Muslimova E, Weng R, Bai Y, Raj S, Hoover-Fong J, Irving M, Rogoff D. Oral Infigratinib Therapy in Children with Achondroplasia. N Engl J Med. 2025 Feb 27;392(9):865-874. doi: 10.1056/NEJMoa2411790. Epub 2024 Nov 18. | |
| 35342457 |
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|
| Infigratinib 0.25 mg/kg | Experimental | Dose Escalation and PK substudy: Infigratinib is provided as minitablets in 2 strengths: 0.1 mg and 1 mg for daily oral administration. The dose and number of minitablets/day will be calculated based on individual participant weight. Doses will be adjusted based on weight changes approximately every 3 months. Dose Expansion: Upon identification of the recommended dose from all cohorts analyzed, an expansion cohort of 20 subjects may begin enrollment to further determine safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of the selected dose. |
|
| Infigratinib 0.032 mg/kg | Drug | Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth. |
|
| Infigratinib 0.064 mg/kg | Drug | Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth. |
|
| Infigratinib 0.128 mg/kg | Drug | Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth. |
|
| Infigratinib 0.25 mg/kg | Drug | Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth. |
|
| 21 days |
| Up to 18 months |
| Absolute and change from baseline in weight (kg) | Up to 18 months |
| Absolute and change from baseline in sitting height (cm) | Up to 18 months |
| Absolute and change from baseline in head circumference (cm) | Up to 18 months |
| Absolute and change from baseline in upper and lower arm length (cm) | Up to 18 months |
| Absolute and change from baseline in thigh length (cm) | Up to 18 months |
| Absolute and change from baseline in knee height (cm) | Up to 18 months |
| Absolute and change from baseline in arm span (cm) | Up to 18 months |
| Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax) | Up to 18 months |
| Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax) | Up to 18 months |
| Changes in pharmacodynamic parameters by assessing collagen X marker | Up to 18 months |
| Wilmington |
| Delaware |
| 19803 |
| United States |
| Johns Hopkins School of Medicine | Baltimore | Maryland | 21211 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Murdoch Children's Hospital | Parkville | Victoria | 3052 | Australia |
| Stollery Children's Hospital | Edmonton | Alberta | T6G 2H7 | Canada |
| Hopital Femme Mere Enfant | Lyon | France |
| Hopital Necker-Enfants Malades | Paris | France |
| Hopital des Enfants | Toulouse | France |
| Hospital Universitario La Paz | Madrid | 24086 | Spain |
| Hospital Universitario Virgen de la Victoria | Málaga | Spain |
| Vithas Hospital San José | Vitoria-Gasteiz | Álava | 01012 | Spain |
| Sheffield Children's Hospital | Sheffield | England | S10 2TH | United Kingdom |
| Birmingham Children's Hospital | Birmingham | United Kingdom |
| University Hospitals Bristol and Weston NHS Foundation Trust | Bristol | BS1 3NU | United Kingdom |
| Queen Elizabeth University Hospital | Glasgow | United Kingdom |
| Evelina London Children's Hospital | London | United Kingdom |
| Manchester University Children's Hospital | Manchester | United Kingdom |
| Derived |
| Savarirayan R, De Bergua JM, Arundel P, McDevitt H, Cormier-Daire V, Saraff V, Skae M, Delgado B, Leiva-Gea A, Santos-Simarro F, Salles JP, Nicolino M, Rossi M, Kannu P, Bober MB, Phillips J 3rd, Saal H, Harmatz P, Burren C, Gotway G, Cho T, Muslimova E, Weng R, Rogoff D, Hoover-Fong J, Irving M. Infigratinib in children with achondroplasia: the PROPEL and PROPEL 2 studies. Ther Adv Musculoskelet Dis. 2022 Mar 21;14:1759720X221084848. doi: 10.1177/1759720X221084848. eCollection 2022. |
| ID | Term |
|---|---|
| D000130 | Achondroplasia |
| D009085 | Mucopolysaccharidosis IV |
| D004392 | Dwarfism |
| D001847 | Bone Diseases |
| D001848 | Bone Diseases, Developmental |
| D009140 | Musculoskeletal Diseases |
| D010009 | Osteochondrodysplasias |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C568950 | infigratinib |
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