Clinical trial NCT06842355: A Study of TYRA-300 in Children With Achondroplasia: BEACH301
Official title: A Multicenter, Phase 2, Dose-Escalation/Dose-Expansion Study of TYRA-300 in Children With Achondroplasia With Open Growth Plates: BEACH301
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Achondroplasia
Lead sponsor: Tyra Biosciences, Inc
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 92
Sex: ALL
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: Up to 12 months
measure: Change from baseline in annualized growth velocity (Cohort 1)
timeFrame: 12 months
Secondary outcomes:
measure: Change from baseline in annualized growth velocity (Cohort 1)
timeFrame: 6 months
measure: Change from baseline in height z-score (Cohort 1)
timeFrame: 6 and 12 months
measure: Pharmacokinetics: maximum plasma concentration (Cmax)
timeFrame: 15 days
measure: Pharmacokinetics: time to reach maximum plasma concentration (Tmax)
timeFrame: 15 days
measure: Pharmacokinetics: area under the plasma concentration-time curve (AUC)
timeFrame: 15 days
measure: Pharmacokinetics: half-life of TYRA-300 (t1/2)
timeFrame: 15 days
measure: Pharmacokinetics: apparent total clearance (CL/F)
timeFrame: 15 days
measure: Pharmacokinetics: apparent volume of distribution (Vd/F)
timeFrame: 15 days
measure: Change from baseline in annualized growth velocity (Cohort 2)
timeFrame: 6 and 12 months
measure: Change from baseline in height z-score (Cohort 2)
timeFrame: 6 and 12 months
measure: Change from baseline in standing height (cm)
timeFrame: 6 and 12 months
measure: Change from baseline in sitting height (cm)
timeFrame: 6 and 12 months
measure: Change from baseline in upper and lower arm length (cm)
timeFrame: 6 and 12 months
measure: Change from baseline in tibial length (cm)
timeFrame: 6 and 12 months
measure: Change from baseline in femur length (cm)
timeFrame: 6 and 12 months
measure: Change from baseline in arm span proportionality (arm span/height ratio)
timeFrame: 6 and 12 months
measure: Change from baseline in upper segment/lower segment ratio
timeFrame: 6 and 12 months
measure: Change from baseline in elbow extension
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Kissimmee
country: United States
facility: Rare Disease Research
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Hillsborough
country: United States
facility: Rare Disease Research
state: North Carolina
Study officials:
affiliation: Tyra Biosciences
name: Doug Warner, MD
role: STUDY_CHAIR
References: