An Interventional Study of Infigratinib in Children With Hypochondroplasia (HCH)

A Phase 2/3, Multicenter, Open-Label Phase Followed by a Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children With Hypochondroplasia: ACCEL 2/3

ACCEL2/3 is a Phase 2/3 study. The purpose of the Phase 2 portion of the study (ACCEL2/3) is to evaluate the efficacy and safety of infigratinib in children with hypochondroplasia (HCH) receiving infigratinib at one of two doses, who have completed at least 26 weeks of participation in QED-sponsored ACCEL (QBGJ398-004).

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypochondroplasia
• Intervention / Treatment: Drug: infigratinib 0.128 mg/kg/day; Drug: infigratinib 0.25 mg/kg/day

Detailed Description

ACCEL 2/3 is a Phase 2/3 study that comprises of 2 portions. The Phase 2 portion is an open-label, portion in children with HCH aged 5 to 11 years old followed by a Phase 3 portion which is double-blind, placebo-controlled in children with HCH aged >3 years old to <18 years old.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute - The Royal Children's Hospital Melbourne
• Canada
  • Ontario
    • London, Ontario, Canada, N6C 2R5
      • London Health Services Centre - Children's Hospital of Western Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine
• France
  • France
    • Bron, France, France, 69677
      • Hopital Femme Mere Enfant
    • Paris, France, France, 75015
      • Hopital universitaire Necker-Enfants Malades
    • Toulouse, France, France, 31059
      • Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital des Enfants
• Norway
  • Norway
    • Bergen, Norway, Norway, 5021
      • Haukeland University Hospital
    • Oslo, Norway, Norway, 0372
      • Paediatric Clinical Research Unit at Oslo University Hospital
• Portugal
  • Portugal
    • Coimbra, Portugal, Portugal, 3000-602
      • Hospital Pediátrico de Coimbra
• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 229899
      • KK Women's and Children's Hospital
• Spain
  • Spain
    • Vitoria-Gasteiz, Spain, Spain, 01010
      • Unidad de Cirugía Artroscopica, Hopsital MIKS
• Sweden
  • Sweden
    • Solna, Sweden, Sweden, 17164
      • Astrid Lindgren Children's Hospital
• United Kingdom
  • England
    • Manchester, England, United Kingdom, M13 9WL
      • Manchester University
    • Sheffield, England, United Kingdom, S10 2TH
      • Sheffield Children's Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Glasgow Clinical Research Facility, Queen Elizabeth University Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Childrens Hospital Colorado
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins School of Medicine
  • Missouri
    • Columbia, Missouri, United States, 65201
      • 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 of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must have completed at least 26 weeks and still be on the observational study (QBGJ398-004).
• Phase 2 portion: Participants 5-11 years of age (inclusive).
• Phase 3 portion: Participants 3 to <18 years of age at screening with growth potential
• Diagnosis of HCH documented clinically by the presence of disproportionate short stature and confirmed with a molecular test.
• Participants are able to swallow oral medication.
• Participants and parent(s), legal guardian(s), or caregiver(s) are willing and able to comply with study visits and study procedures.
• Participants are ambulatory and able to stand without assistance. Sex and Contraceptive/Barrier Requirements
• Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
• If sexually active, participants whether male or female, must be willing to use a highly effective method of contraception, as relevant, while taking study drug and for 1 month after the last dose of study drug.
• Signed informed consent.

Key Exclusion Criteria:

• Participants who have ACH or a short stature condition other than HCH.
• Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
• Current evidence of clinically significant corneal or retinal disorder/keratopathy confirmed by ophthalmic examination.
• Concurrent circumstance, disease, or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations.
• History and/or current evidence of extensive ectopic tissue calcification.
• History of malignancy.
• Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH, HCH, or short stature.
• Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid.
• Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening or guided growth surgery while participating in the study.
• Participants receiving medications which could increase serum phosphorus and/or calcium concentrations
• Clinically significant abnormality in any laboratory test result at screening.
• Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
• Allergy to any components of the study drug.
• Concurrent circumstance, disease, or condition that would interfere with study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 Cohort 1; Oral infigratinib 0.128 mg/kg/day	Drug: infigratinib 0.128 mg/kg/day; Oral infigratinib 0.128 mg/kg/day
Experimental: Phase 2 Cohort 2; Oral infigratinib 0.25 mg/kg/day	Drug: infigratinib 0.25 mg/kg/day; Oral infigratinib 0.25 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline (BL) in Annualized Height Velocity (AHV; cm/year)	26 weeks
Incidence, severity, and seriousness of adverse events (AEs) that require dose reduction or discontinuation	at least 26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in cognitive function (as assessed by age appropriate computerized tests)	52 weeks
Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)	52 weeks
Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)	52 weeks
Change from BL in collagen X marker (CXM) levels	52 weeks
Change from BL in height Z-score (in relation to both HCH and average height tables)	52 weeks
Change from BL in upper to lower body segment ratio (cm)	52 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change from BL in comorbidities associated with HCH	52 weeks
Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Pediatric Quality of Life Inventory [PedsQL tool])	52 weeks
Evaluate treatment benefit as assessed by qualitative interviews	52 weeks

Collaborators and Investigators

• Sponsor: QED Therapeutics, a BridgeBio company

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 12, 2025

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: quality of life; bone diseases; growth; dwarfism; genetic diseases; functional abilities; FGFR3; skeletal dysplasia; hypochondroplasia; AGV; congenital; musculoskeletal diseases; Pathogenic variants; endochondral ossification; HCH; shortened proximal limbs; fibroblast growth factor receptor 3; endochondral bone formation; osteochondrodysplasia; disproportionate short stature; annualized growth velocity; annualized height velocity; AHV
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolism, Inborn Errors; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Bone Diseases, Developmental; 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; Osteochondrodysplasias; Mucopolysaccharidosis IV; Hypochondroplasia; Antineoplastic Agents; infigratinib
• Other Study ID Numbers: QBGJ398-304

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