A Study of TYRA-300 in Children With Achondroplasia: BEACH301

This is a Phase 2, multicenter, open-label, dose-escalation study to determine the safety, tolerability, and identify potentially effective dose(s) of TYRA-300, a fibroblast growth factor receptor (FGFR)-3 selective tyrosine kinase inhibitor, in children 3 to 10 years of age with achondroplasia with open growth plates that will examine three cohorts of children: the Sentinel Safety Cohort, Cohort 1, and Cohort 2.

Inclusion criteria

• Aged 3 to 10 years old (inclusive) at the time of consent.
• Informed consent provided by parent(s) or legal guardian(s). As study participants are less than 18 years old, participants are willing and able to provide written assent (where applicable and required).
• Molecular diagnosis of achondroplasia (FGFR3 G380R).
• Radiographically confirmed open growth plates at Screening, as determined by bone age X-ray.
• Able to stand and ambulate independently.
• Able to take oral medication.
• Sentinel Safety Cohort only: aged 5 to 10 years old (inclusive).
• Cohort 1 only: aged 3 to 10 years old (inclusive) and are naive to prior growth accelerating therapy.
• Cohort 2 only: aged 3 to 10 years old (inclusive) and have received prior growth accelerating therapy.

Exclusion criteria

• Presence or history of any concurrent disease or condition that would interfere with study participation, safety evaluations, or any uncontrolled or untreated condition that could impact pediatric growth.
• Diagnosis of endocrine condition that alters calcium/phosphate homeostasis.
• Prior limb lengthening surgery or planned or expected to have limb lengthening surgery while enrolled in the study.
• Taking medications that are strong inhibitors or inducers of cytochrome P450 (Cyp) 3A4.
• History or current evidence of corneal or retinal disorder/keratopathy.
• Presence of guided growth hardware/8 plates. Planned or anticipated orthopedic surgeries.