an interventional study of infigratinib in children with hypochondroplasia

Conditions: Hypochondroplasia

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).

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.

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