Extension Study of Infigratinib in Children With Achondroplasia (ACH)

Phase 2, Open-Label, Long-Term, Extension (OLE) Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL OLE

This is a Phase 2, multicenter, open-label, extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of infigratinib, an FGFR 1-3-selective tyrosine kinase inhibitor, in subjects with ACH who previously completed a QED-sponsored interventional study, and potentially in additional subjects who are naïve to infigratinib treatment. Quality of Life assessments for this subject population will also be evaluated. Treatment-naïve subjects must have at least a 6-month period of growth assessment in study QBGJ398-001 (PROPEL) and will be enrolled in this OLE study only after a dose to be explored further is identified in Phase 2 Study QBGJ398-201 and subjects are not otherwise eligible to enroll in another QED-sponsored Phase 2 or Phase 3 ACH study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Achondroplasia
• Intervention / Treatment: Drug: Infigratinib; Drug: Infigratinib

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina, C1245AAM
      • Hospital de Pediatría SAMIC Prof. Dr. Juan P. Garrahan
• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Hospital
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6C 2B7
      • Stollery Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital - London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre Hospitalier Universitaire Sainte-Justine
• France
  • Lyon, France, 69500
    • Hopital Femme Mere Enfant
  • Paris, France, 75743
    • Hôpital Necker-Enfants Malades
  • Toulouse, France, 31300
    • Hôpital des Enfants
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Roma, Italy, 00168
    • Policlinico A. Gemelli IRCCS
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Oslo, Norway, 0372
    • Oslo University Hospital
• Singapore
  • Singapore, Singapore, 229899
    • KK Women's and Children's Hosptial
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Álava
    • Vitoria-Gasteiz, Álava, Spain, 01012
      • Hospital Vithas San Jose
• United Kingdom
  • Birmingham, United Kingdom, B5 6NH
    • Birmingham Women's and Children's NHS Foundation Trust
  • Bristol, United Kingdom, BS2 8AE
    • University Hospitals Bristol and Weston NHS Foundation Trust
  • Glasgow, United Kingdom, G12 0XH
    • Queen Elizabeth University Hospital
  • London, United Kingdom, SE1 7EH
    • St. Thomas' Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester University Children's Hospital
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • USCF Benioff Children's Hospital, Oakland
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Alfred I. Dupont Hospital for Children
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University Hospital and UW Health Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Key Rollover Subjects Inclusion Criteria:

1. Pediatric subjects with ACH who have completed a previous QED-sponsored interventional study with infigratinib.
2. Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
3. Subjects are able to swallow oral medication.
4. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
5. If sexually active, subject must be willing to use a highly effective method of contraception while taking study drug and for 1 month after the last dose of study drug.
6. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parent(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed.

Key Rollover Subjects Exclusion Criteria:

1. Subject has concurrent circumstance, disease, or condition that, in the view of the PI and/or sponsor, would interfere with study participation or safety evaluations.
2. Subjects who developed a medical condition that will require the initiation of treatment with a prohibited medication.
3. Subjects prematurely discontinued a prior QED-sponsored interventional study with infigratinib
4. Current participation in an ongoing clinical study with a sponsor other than QED
5. Subjects that have reached final height or near final height.

Key Inclusion Criteria for Treatment Naïve Subjects

1. Subject must be 3 to <18 years of age at screening and have growth potential.
2. Subjects and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
3. Subjects are able to swallow oral medication.
4. Subjects who have a diagnosis of ACH, documented clinically and confirmed by genetic testing.
5. Subjects have at least a 6-month period of growth assessment in the PROPEL study (Protocol QBGJ398 001) before study entry.
6. Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
7. If sexually active, subject must be willing to use a highly effective method of contraception while taking study drug and for 1 month after the last dose of study drug.
8. The PI, or a person designated by the PI, will obtain written informed consent from each subject's parent(s), legal guardian(s), or caregiver(s) and the subject's assent, when applicable, before any study-specific activity is performed.

Key Exclusion Criteria for Treatment Naïve Subjects

1. Subjects who have hypochondroplasia or short stature condition other than ACH (e.g., trisomy 21, pseudoachondroplasia, psychosocial short stature).
2. Subjects who have significant concurrent disease or condition that, in the view of the PI and/or sponsor, would represent an increased risk to the subject or would interfere with study participation or safety evaluations.
3. Subjects who have a history of malignancy.
4. Subjects who are currently receiving treatment with agents that are known strong inducers or inhibitors of cytochrome P450 (CYP) 3A4.
5. Subjects who discontinued treatment with prohibited medications for at least 5 half-lives before screening are eligible.
6. Subjects who have received treatment with growth hormone, insulin-like growth factor 1 (IGF 1), anabolic steroids or any investigational or approved drug for the treatment of ACH in the previous 6 months.
7. Subjects who have significant abnormality in screening laboratory results.
8. Subjects who have had a fracture within 12 months of screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2: Treatment naïve subjects; Children naïve to infigratinib	Drug: Infigratinib; Infigratinib minitablets or sprinkle capsules to be administered by mouth. In subjects that completed a prior study with infigratinib, the starting dose will be the same as the last dose received in the prior interventional study with infigratinib. Infigratinib dose may be adjusted to 0.25 mg/kg/day (the dose selected to be explored further in the dose escalation portion of Phase 2 study QBGJ398-201 (PROPEL 2)).; Drug: Infigratinib; Infigratinib sprinkle capsules to be administered by mouth. Starting dose for the subjects naïve to Infigratinib will be 0.25 mg/kg/day (the dose selected to be explored further in the dose escalation portion of Phase 2 study QBGJ398-201 (PROPEL 2)).
Experimental: Arm 1: Rollover subjects; Children who have completed QED-sponsored interventional study with infigratinib (Phase 2 or Phase 3)	Drug: Infigratinib; Infigratinib minitablets or sprinkle capsules to be administered by mouth. In subjects that completed a prior study with infigratinib, the starting dose will be the same as the last dose received in the prior interventional study with infigratinib. Infigratinib dose may be adjusted to 0.25 mg/kg/day (the dose selected to be explored further in the dose escalation portion of Phase 2 study QBGJ398-201 (PROPEL 2)).; Drug: Infigratinib; Infigratinib sprinkle capsules to be administered by mouth. Starting dose for the subjects naïve to Infigratinib will be 0.25 mg/kg/day (the dose selected to be explored further in the dose escalation portion of Phase 2 study QBGJ398-201 (PROPEL 2)).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of treatment emergent adverse events (TEAE) and serious TEAE	10 years
Changes over time in height Z-score in relation to ACH and non-ACH growth charts	10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes over time in body proportions	10 years
Changes over time in weight z-score	10 years
Changes overtime in BMI	10 years
Age of puberty onset and time to Tanner stage ≥4	10 years
Changes over time in number of episodes of otitis media per year	10 years
Changes over time in number of episodes and/or severity of sleep apnea	10 years
Changes over time in skeletal abnormalities of the lower extremities and spine	10 years
Changes in functional abilities as evaluated by Functional Independence Measure for Children (WeeFIM)	10 years
Changes in cognitive functions assessed by age-appropriate computerized tests	10 years
Changes over time in absolute height velocity, expressed as height velocity Z-score in relation to ACH and non ACH growth charts	10 years
Changes over time in range of motion (elbow)	10 years
Changes in health-related Quality of life [HRQoL] as assessed by Pediatric Quality of Life Inventory (PedsQL)	10 years
Changes in health-related Quality of life [HRQoL] as assessed by Quality of Life in Short Stature Youth questionnaire (QoLISSY)	10 years
Overall pain as assessed by Numeric Rating Scale for pain (Pain-NRS)	10 years
Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Severity (PGI-S)	10 years
Severity of the physical functioning challenges as assessed by Patient/Parent Global Impression of Change (PGI-C)	10 years
Subject and caregiver evaluation of treatment benefit as assessed by a qualitative interview	10 years

Collaborators and Investigators

• Sponsor: QED Therapeutics, a BridgeBio company
• Investigators: Study Director: QED Therapeutics SVP, Clinical Development, QED Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Estimated): October 31, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Growth; Tyrosine kinase inhibitor; FGFR3; Genetic diseases; Bone disease; Skeletal dysplasia; Endochondral ossification; Fibroblast growth factor receptor 3; Endochondral bone formation; Musculoskeletal diseases; Osteochondrodysplasia; Achondroplasia (ACH); Quality of life in achondroplasia; Functionality in achondroplasia; Long - term treatment; Annualized height velocity; Short-limb disproportionate stature; Treatment option
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; Dwarfism; Mucopolysaccharidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Achondroplasia; Osteochondrodysplasias; Mucopolysaccharidosis IV; Antineoplastic Agents; infigratinib
• Other Study ID Numbers: QBGJ398-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No