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

Phase 2

Recruiting

• Conditions: Achondroplasia
• Interventions: Drug: TYRA-300 0.375 mg/kg; Drug: TYRA-300 0.125 mg/kg; Drug: TYRA-300 0.25 mg/kg; Drug: TYRA-300 0.50 mg/kg

• Registration Number: NCT06842355
• Lead Sponsor: Tyra Biosciences, Inc

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and identify potentially effective dose(s) of TYRA-300 in children with achondroplasia with open growth plates.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2025-01-29
• Study First Submitted QC: 2025-02-18
• Status Verified: 2025-03
• Study Start: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-26
• Last Update Posted: 2025-03-27
• Primary Completion: 2030-01
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 92

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
TYRA-300 0.375 mg/kg	TYRA-300 0.375 mg/kg	TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
TYRA-300 0.125 mg/kg	TYRA-300 0.125 mg/kg	TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
TYRA-300 0.25 mg/kg	TYRA-300 0.25 mg/kg	TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.
TYRA-300 0.50 mg/kg	TYRA-300 0.50 mg/kg	TYRA-300 is provided as sprinkle capsules/mini-tablets. The total dose will be calculated based on the participant's weight. Weight adjustments will be made every 3 months.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-related adverse events as assessed by CTCAE v5.0	Up to 12 months
Change from baseline in annualized growth velocity (Cohort 1)	12 months

Secondary Outcome Measures

Name	Time	Method
Change from baseline in annualized growth velocity (Cohort 1)	6 months
Change from baseline in height z-score (Cohort 1)	6 and 12 months
Pharmacokinetics: maximum plasma concentration (Cmax)	15 days
Pharmacokinetics: time to reach maximum plasma concentration (Tmax)	15 days
Pharmacokinetics: area under the plasma concentration-time curve (AUC)	15 days
Pharmacokinetics: half-life of TYRA-300 (t1/2)	15 days
Pharmacokinetics: apparent total clearance (CL/F)	15 days
Pharmacokinetics: apparent volume of distribution (Vd/F)	15 days
Change from baseline in annualized growth velocity (Cohort 2)	6 and 12 months
Change from baseline in height z-score (Cohort 2)	6 and 12 months
Change from baseline in standing height (cm)	6 and 12 months
Change from baseline in sitting height (cm)	6 and 12 months
Change from baseline in upper and lower arm length (cm)	6 and 12 months
Change from baseline in tibial length (cm)	6 and 12 months
Change from baseline in femur length (cm)	6 and 12 months
Change from baseline in arm span proportionality (arm span/height ratio)	6 and 12 months
Change from baseline in upper segment/lower segment ratio	6 and 12 months
Change from baseline in elbow extension	6 and 12 months

Trial Locations

Locations (1)

Rare Disease Research; 🇺🇸 Hillsborough, North Carolina, United States