An Interventional Study of Infigratinib in Children With Hypochondroplasia

Phase 2

• Conditions: Hypochondroplasia
• Interventions: Drug: infigratinib 0.128 mg/kg/day; Drug: infigratinib 0.25 mg/kg/day

• Registration Number: NCT06873035
• Lead Sponsor: QED Therapeutics, Inc.

Brief Summary

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, of who have completed at least 26 weeks of participation in QED-sponsored ACCEL (QBGJ398-004).

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 Timeline

• Study First Submitted: 2025-02-18
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-06
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-04-01
• Study Start: 2025-05
• Primary Completion: 2027-01
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Cohort 1	infigratinib 0.128 mg/kg/day	infigratinib (0.128 mg/kg/day)
Phase 2 Cohort 2	infigratinib 0.25 mg/kg/day	infigratinib (0.25 mg/kg/day)

Primary Outcome Measures

Name	Time	Method
Change from baseline (BL) in Annualized Height Velocity (AHV; cm/year)	52 weeks
Incidence, severity, and seriousness of adverse events (AEs) that require dose reduction or discontinuation	52 weeks

Secondary Outcome Measures

Name	Time	Method
Change from BL in height Z-score	52 weeks
Change from BL in height z-score [ethnic-specific growth charts may be used if/when applicable and available] of growth and body proportions	52 weeks
Changes in upper to lower body segment ratio (cm)	52 weeks
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

Trial Locations

Locations (22)

Haukeland University Hospital; 🇳🇴 Bergen, Norway

Paediatric Clinical Research Unit at Osla University Hospital; 🇳🇴 Oslo, Norway

Hospital Pediátrico de Coimbra; 🇵🇹 Coimbra, Portugal

Hospital Vithas San Jose; 🇪🇸 Vitoria-gasteiz, Spain

Astrid Lindgren Children's Hospital; 🇸🇪 Solna, Sweden

Manchester University; 🇬🇧 Manchester, United Kingdom

Sheffield Children's Hospital; 🇬🇧 Sheffield, United Kingdom

Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine; 🇨🇦 Montréal, Quebec, Canada

UCSF Benioff Children's Hospital; 🇺🇸 Oakland, California, United States

Childrens Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Children's National Hospital; 🇺🇸 Washington, District of Columbia, United States

Johns Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States

University of Missouri; 🇺🇸 Columbia, Missouri, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic; 🇺🇸 Madison, Wisconsin, United States

KK Women's and Children's Hospital; 🇸🇬 Singapore, Singapore

Murdoch Children's Research Institute; 🇦🇺 Parkville, Victoria, Australia

London Health Services Center - Children's Hospital of Western Ontario; 🇨🇦 London, Ontario, Canada

Children's Hospital of Eastern Ontario Research Institute; 🇨🇦 Ottawa, Ontario, Canada

Hôpital Femme Mère Enfant; 🇫🇷 Bron, France

Hôpital Universitaire Necker-Enfants Malades; 🇫🇷 Paris, France

Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital des Enfants; 🇫🇷 Toulouse, France