Hypochondroplasia
Conditions
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, Pathogenic variants
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, 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.
Interventions
DRUGinfigratinib 0.128 mg/kg/day
Oral infigratinib 0.128 mg/kg/day
Oral infigratinib 0.25 mg/kg/day
Sponsors
QED Therapeutics, a BridgeBio company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
3 Years to 18 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Countries
Australia, Canada, France, Norway, Portugal, Singapore, Spain, Sweden, United Kingdom, United States
Outcome results
None listed