Study of Infigratinib in Children With Achondroplasia

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

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 Overview

• Status: Completed
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: Infigratinib 0.016 mg/kg; Drug: Infigratinib 0.032 mg/kg; Drug: Infigratinib 0.064 mg/kg; Drug: Infigratinib 0.128 mg/kg; Drug: Infigratinib 0.25 mg/kg

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2H7
      • Stollery Children's Hospital
• France
  • Lyon, France
    • Hôpital Femme Mère Enfant
  • Paris, France
    • Hôpital Necker-Enfants Malades
  • Toulouse, France
    • Hôpital des Enfants
• Spain
  • Madrid, Spain, 24086
    • Hospital Universitario La Paz
  • Málaga, Spain
    • Hospital Universitario Virgen de la Victoria
  • Álava
    • Vitoria-Gasteiz, Álava, Spain, 01012
      • Vithas Hospital San Jose
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Children's Hospital
  • Bristol, United Kingdom, BS1 3NU
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • London, United Kingdom
    • Evelina London Children's Hospital
  • Manchester, United Kingdom
    • Manchester University Children's Hospital
  • England
    • Sheffield, England, United Kingdom, S10 2TH
      • Sheffield Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94618
      • UCSF Benioff Children's Hospital
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Alfred I. Dupont Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21211
      • Johns Hopkins School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent by participant or parent(s) or legally authorized representative (LAR) and signed informed assent by the participant (when applicable).
2. Diagnosis of ACH, documented clinically and confirmed by genetic testing.
3. At least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398-001) before study entry.
4. Ambulatory and able to stand without assistance
5. Able to swallow oral medication.

Exclusion Criteria:

1. Hypochondroplasia or short stature condition other than ACH.
2. In females, having had their menarche.
3. Height < -2 or > +2 standard deviations for age and sex based on reference tables on growth in children with ACH.
4. Significant concurrent disease or condition that, in the view of the Investigator and/or Sponsor, would confound assessment of efficacy or safety of infigratinib.
5. Current evidence of corneal or retinal disorder/keratopathy.
6. History of malignancy.
7. Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration.
8. 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.
9. Treatment with a C-type natriuretic peptide (CNP) analog, fibroblast growth factor (FGF) ligand trap, or treatment targeting FGFR inhibition at any time.
10. Regular long-term treatment (>3 weeks) with oral corticosteroids (low-dose ongoing inhaled steroid for asthma is acceptable).
11. Treatment with any other investigational product or investigational medical device for the treatment of ACH or short stature.
12. Previous limb-lengthening surgery or guided growth surgery.
13. Fracture within 12 months of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infigratinib 0.016 mg/kg; 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.	Drug: Infigratinib 0.016 mg/kg; 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.
Experimental: Infigratinib 0.032 mg/kg; 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.	Drug: Infigratinib 0.032 mg/kg; Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Experimental: Infigratinib 0.064 mg/kg; 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.	Drug: Infigratinib 0.064 mg/kg; Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Experimental: Infigratinib 0.128 mg/kg; 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.	Drug: Infigratinib 0.128 mg/kg; Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.
Experimental: Infigratinib 0.25 mg/kg; 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.	Drug: Infigratinib 0.25 mg/kg; Subsequent cohort dose escalation based on protocol-specific criteria. Infigratinib tablets to be administered by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)	21 days

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: QED Therapeutics, Inc., a Bridgebio company
• Investigators: Study Director: QED Therapeutics VP, Clinical Development, QED Therapeutics

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2020
• Primary Completion (Actual): October 21, 2024
• Study Completion (Actual): October 21, 2024

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: February 10, 2020
• First Posted (Actual): February 11, 2020

Study Record Updates

• Last Update Posted (Estimated): October 22, 2025
• Last Update Submitted That Met QC Criteria: October 19, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: dwarfism; FGFR3; Bone disease; Inborn; ACH; Skeletal dysplasia; Endochondral ossification; Shortened proximal limbs; Fibroblast growth factor receptor 3; Endochondral bone formation; Short-limb disproportionate dwarfism; Bone diseases, developmental; Musculoskeletal diseases; Osteochondrodysplasia; Genetic diseases, inborn
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolism, Inborn Errors; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Dwarfism; Achondroplasia; Osteochondrodysplasias; Mucopolysaccharidosis IV; Bone Diseases, Developmental; Antineoplastic Agents; infigratinib
• Other Study ID Numbers: QBGJ398-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes