Ignite Creation Date:
2025-12-24 @ 11:52 PM
Ignite Modification Date:
2026-03-06 @ 12:27 AM
Study NCT ID:
NCT04265651
Status:
COMPLETED
Last Update Posted:
2025-10-22
First Post:
2020-01-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Infigratinib in Children With Achondroplasia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000130', 'term': 'Achondroplasia'}, {'id': 'D009085', 'term': 'Mucopolysaccharidosis IV'}, {'id': 'D004392', 'term': 'Dwarfism'}, {'id': 'D001847', 'term': 'Bone Diseases'}, {'id': 'D001848', 'term': 'Bone Diseases, Developmental'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D010009', 'term': 'Osteochondrodysplasias'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}], 'ancestors': [{'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D009083', 'term': 'Mucopolysaccharidoses'}, {'id': 'D002239', 'term': 'Carbohydrate Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D016464', 'term': 'Lysosomal Storage Diseases'}, {'id': 'D017520', 'term': 'Mucinoses'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C568950', 'term': 'infigratinib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SEQUENTIAL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 84}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-03-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'dispFirstSubmitDate': '2025-10-19', 'completionDateStruct': {'date': '2024-10-21', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-10-19', 'studyFirstSubmitDate': '2020-01-29', 'studyFirstSubmitQcDate': '2020-02-10', 'dispFirstPostDateStruct': {'date': '2025-03-26', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2025-10-22', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2020-02-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-10-21', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of treatment-emergent adverse events (TEAEs) that lead to dose decrease or discontinuation', 'timeFrame': 'Up to 18 months'}, {'measure': 'Change from baseline in annualized height velocity', 'timeFrame': 'Up to 18 months'}, {'measure': 'PK parameters of infigratinib (Cmax- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (Clast- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (Tmax- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (AUC24- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (T1/2- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (AUCinf- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (CL/F- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (Vz/F- PK substudy only)', 'timeFrame': '21 days'}, {'measure': 'PK parameters of infigratinib (Racc- PK substudy only)', 'timeFrame': '21 days'}], 'secondaryOutcomes': [{'measure': 'Incidence of adverse events (AEs) and serious adverse events (SAEs) as a measure of safety and tolerability', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute height velocity (annualized to cm/year), expressed numerically and as Z-score in relation to ACH and non-ACH tables', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in weight (kg)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in sitting height (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in head circumference (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in upper and lower arm length (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in thigh length (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in knee height (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Absolute and change from baseline in arm span (cm)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)', 'timeFrame': 'Up to 18 months'}, {'measure': 'Changes in pharmacodynamic parameters by assessing collagen X marker', 'timeFrame': 'Up to 18 months'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Skeletal dysplasia', 'Endochondral ossification', 'ACH', 'Shortened proximal limbs', 'Fibroblast growth factor receptor 3', 'FGFR3', 'Endochondral bone formation', 'Short-limb disproportionate dwarfism', 'dwarfism', 'Bone disease', 'Bone diseases, developmental', 'Musculoskeletal diseases', 'Osteochondrodysplasia', 'Genetic diseases, inborn', 'Inborn'], 'conditions': ['Achondroplasia']}, 'referencesModule': {'references': [{'pmid': '39555818', 'type': 'DERIVED', 'citation': '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.'}, {'pmid': '35342457', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '11 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).\n2. Diagnosis of ACH, documented clinically and confirmed by genetic testing.\n3. At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.\n4. Ambulatory and able to stand without assistance\n5. Able to swallow oral medication.\n\nExclusion Criteria:\n\n1. Hypochondroplasia or short stature condition other than ACH.\n2. In females, having had their menarche.\n3. Height \\< -2 or \\> +2 standard deviations for age and sex based on reference tables on growth in children with ACH.\n4. Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib.\n5. Current evidence of corneal or retinal disorder/keratopathy.\n6. History of malignancy.\n7. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.\n8. Treatment with growth hormone, insulin-like growth factor 1 (IGF-1), or anabolic steroids in the previous 6 months or long-term treatment (\\>3 months) at any time.\n9. Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.\n10. Regular long-term treatment (\\>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).\n11. Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.\n12. Previous limb-lengthening surgery or guided growth surgery.\n13. Fracture within 12 months of screening.'}, 'identificationModule': {'nctId': 'NCT04265651', 'briefTitle': 'Study of Infigratinib in Children With Achondroplasia', 'organization': {'class': 'INDUSTRY', 'fullName': 'QED Therapeutics, a BridgeBio company'}, 'officialTitle': 'Phase 2, Open-Label, Dose-Escalation and Dose-Expansion Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL 2', 'orgStudyIdInfo': {'id': 'QBGJ398-201'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Infigratinib 0.016 mg/kg', 'description': 'Dose Escalation:\n\nInfigratinib 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.', 'interventionNames': ['Drug: Infigratinib 0.016 mg/kg']}, {'type': 'EXPERIMENTAL', 'label': 'Infigratinib 0.032 mg/kg', 'description': 'Dose Escalation and PK substudy:\n\nInfigratinib 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.', 'interventionNames': ['Drug: Infigratinib 0.032 mg/kg']}, {'type': 'EXPERIMENTAL', 'label': 'Infigratinib 0.064 mg/kg', 'description': 'Dose Escalation and PK substudy:\n\nInfigratinib 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.', 'interventionNames': ['Drug: Infigratinib 0.064 mg/kg']}, {'type': 'EXPERIMENTAL', 'label': 'Infigratinib 0.128 mg/kg', 'description': 'Dose Escalation and PK substudy:\n\nInfigratinib 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.', 'interventionNames': ['Drug: Infigratinib 0.128 mg/kg']}, {'type': 'EXPERIMENTAL', 'label': 'Infigratinib 0.25 mg/kg', 'description': 'Dose Escalation and PK substudy:\n\nInfigratinib 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.\n\nDose Expansion:\n\nUpon 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.', 'interventionNames': ['Drug: Infigratinib 0.25 mg/kg']}], 'interventions': [{'name': 'Infigratinib 0.016 mg/kg', 'type': 'DRUG', 'description': 'Initial cohort dose of infigratinib at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.\n\nInfigratinib tablets to be administered by mouth.', 'armGroupLabels': ['Infigratinib 0.016 mg/kg']}, {'name': 'Infigratinib 0.032 mg/kg', 'type': 'DRUG', 'description': 'Subsequent cohort dose escalation based on protocol-specific criteria.\n\nInfigratinib tablets to be administered by mouth.', 'armGroupLabels': ['Infigratinib 0.032 mg/kg']}, {'name': 'Infigratinib 0.064 mg/kg', 'type': 'DRUG', 'description': 'Subsequent cohort dose escalation based on protocol-specific criteria.\n\nInfigratinib tablets to be administered by mouth.', 'armGroupLabels': ['Infigratinib 0.064 mg/kg']}, {'name': 'Infigratinib 0.128 mg/kg', 'type': 'DRUG', 'description': 'Subsequent cohort dose escalation based on protocol-specific criteria.\n\nInfigratinib tablets to be administered by mouth.', 'armGroupLabels': ['Infigratinib 0.128 mg/kg']}, {'name': 'Infigratinib 0.25 mg/kg', 'type': 'DRUG', 'description': 'Subsequent cohort dose escalation based on protocol-specific criteria.\n\nInfigratinib tablets to be administered by mouth.', 'armGroupLabels': ['Infigratinib 0.25 mg/kg']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94618', 'city': 'Oakland', 'state': 'California', 'country': 'United States', 'facility': "UCSF Benioff Children's Hospital", 'geoPoint': {'lat': 37.80437, 'lon': -122.2708}}, {'zip': '19803', 'city': 'Wilmington', 'state': 'Delaware', 'country': 'United States', 'facility': 'Nemours Alfred I. Dupont Hospital for Children', 'geoPoint': {'lat': 39.74595, 'lon': -75.54659}}, {'zip': '21211', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins School of Medicine', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '45229', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': "Cincinnati Children's Hospital Medical Center", 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '37232', 'city': 'Nashville', 'state': 'Tennessee', 'country': 'United States', 'facility': 'Vanderbilt University Medical Center', 'geoPoint': {'lat': 36.16589, 'lon': -86.78444}}, {'zip': '3052', 'city': 'Parkville', 'state': 'Victoria', 'country': 'Australia', 'facility': "Murdoch Children's Hospital", 'geoPoint': {'lat': -37.78333, 'lon': 144.95}}, {'zip': 'T6G 2H7', 'city': 'Edmonton', 'state': 'Alberta', 'country': 'Canada', 'facility': "Stollery Children's Hospital", 'geoPoint': {'lat': 53.55014, 'lon': -113.46871}}, {'city': 'Lyon', 'country': 'France', 'facility': 'Hopital Femme Mere Enfant', 'geoPoint': {'lat': 45.74906, 'lon': 4.84789}}, {'city': 'Paris', 'country': 'France', 'facility': 'Hopital Necker-Enfants Malades', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'city': 'Toulouse', 'country': 'France', 'facility': 'Hopital des Enfants', 'geoPoint': {'lat': 43.60426, 'lon': 1.44367}}, {'zip': '24086', 'city': 'Madrid', 'country': 'Spain', 'facility': 'Hospital Universitario La Paz', 'geoPoint': {'lat': 40.4165, 'lon': -3.70256}}, {'city': 'Málaga', 'country': 'Spain', 'facility': 'Hospital Universitario Virgen de la Victoria', 'geoPoint': {'lat': 36.72016, 'lon': -4.42034}}, {'zip': '01012', 'city': 'Vitoria-Gasteiz', 'state': 'Álava', 'country': 'Spain', 'facility': 'Vithas Hospital San José', 'geoPoint': {'lat': 42.84998, 'lon': -2.67268}}, {'zip': 'S10 2TH', 'city': 'Sheffield', 'state': 'England', 'country': 'United Kingdom', 'facility': "Sheffield Children's Hospital", 'geoPoint': {'lat': 53.38297, 'lon': -1.4659}}, {'city': 'Birmingham', 'country': 'United Kingdom', 'facility': "Birmingham Children's Hospital", 'geoPoint': {'lat': 52.48142, 'lon': -1.89983}}, {'zip': 'BS1 3NU', 'city': 'Bristol', 'country': 'United Kingdom', 'facility': 'University Hospitals Bristol and Weston NHS Foundation Trust', 'geoPoint': {'lat': 51.45523, 'lon': -2.59665}}, {'city': 'Glasgow', 'country': 'United Kingdom', 'facility': 'Queen Elizabeth University Hospital', 'geoPoint': {'lat': 55.86515, 'lon': -4.25763}}, {'city': 'London', 'country': 'United Kingdom', 'facility': "Evelina London Children's Hospital", 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}, {'city': 'Manchester', 'country': 'United Kingdom', 'facility': "Manchester University Children's Hospital", 'geoPoint': {'lat': 53.48095, 'lon': -2.23743}}], 'overallOfficials': [{'name': 'QED Therapeutics VP, Clinical Development', 'role': 'STUDY_DIRECTOR', 'affiliation': 'QED Therapeutics'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'QED Therapeutics, a BridgeBio company', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}