Clinical trial NCT06873035: An Interventional Study of Infigratinib in Children With Hypochondroplasia
Official title: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Hypochondroplasia
Keywords: skeletal dysplasia
endochondral ossification
hypochondroplasia
HCH
shortened proximal limbs
fibroblast growth factor receptor 3
FGFR3
endochondral bone formation
disproportionate short stature
quality of life
dwarfism
bone diseases
musculoskeletal diseases
osteochondrodysplasia
functional abilities
annualized growth velocity
annualized height velocity
growth
genetic diseases
congenital
AHV
AGV
Lead sponsor: QED Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-12
Enrollment: 24
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study comprises an open-label Phase 2 portion to evaluate safety and efficacy in participants receiving infigratinib at one of two doses followed by a Phase 3 randomized, double-blind portion of the dose selected from the Phase 2 portion versus placebo.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline (BL) in Annualized Height Velocity (AHV; cm/year)
timeFrame: 52 weeks
measure: Incidence, severity, and seriousness of adverse events (AEs) that require dose reduction or discontinuation
timeFrame: 52 weeks
Secondary outcomes:
measure: Change from BL in height Z-score
timeFrame: 52 weeks
measure: Change from BL in height z-score [ethnic-specific growth charts may be used if/when applicable and available] of growth and body proportions
timeFrame: 52 weeks
measure: Changes in upper to lower body segment ratio (cm)
timeFrame: 52 weeks
measure: Changes in cognitive function (as assessed by age appropriate computerized tests)
timeFrame: 52 weeks
measure: Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)
timeFrame: 52 weeks
measure: Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)
timeFrame: 52 weeks
measure: Change from BL in collagen X marker (CXM) levels
timeFrame: 52 weeks
Other outcomes:
measure: Change from BL in comorbidities associated with HCH
timeFrame: 52 weeks
measure: Change from BL in Health-related Quality of Life (HRQoL) (as assessed by Pediatric Quality of Life Inventory [PedsQL tool])
timeFrame: 52 weeks
measure: Evaluate treatment benefit as assessed by qualitative interviews
timeFrame: 52 weeks
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Childrens Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Madison
country: United States
facility: University of Wisconsin Madison - Waisman Center Bone Dysplasia Clinic
state: Wisconsin
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: London
country: Canada
facility: London Health Services Center - Children's Hospital of Western Ontario
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario Research Institute
state: Ontario
city: Montréal
country: Canada
facility: Université de Montréal - Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Bron
country: France
facility: Hôpital Femme Mère Enfant
city: Paris
country: France
facility: Hôpital Universitaire Necker-Enfants Malades
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire (CHU) de Toulouse - Hôpital des Enfants
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Paediatric Clinical Research Unit at Osla University Hospital
city: Coimbra
country: Portugal
facility: Hospital Pediátrico de Coimbra
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Vitoria-gasteiz
country: Spain
facility: Hospital Vithas San Jose
city: Solna
country: Sweden
facility: Astrid Lindgren Children's Hospital
city: Manchester
country: United Kingdom
facility: Manchester University
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital
Study officials:
References: