Achondroplasia
Conditions
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.
Interventions
DRUGTYRA-300 0.125 mg/kg
Initial dose level of TYRA-300 per protocol, subsequent dose level escalations will occur based on criteria outlined in the protocol.
DRUGTYRA-300 0.25 mg/kg
Subsequent dose level escalations will occur based on criteria outlined in the protocol.
DRUGTYRA-300 0.375 mg/kg
Subsequent dose level escalations will occur based on criteria outlined in the protocol.
DRUGTYRA-300 0.50 mg/kg
Subsequent dose level escalations will occur based on criteria outlined in the protocol.
DRUGTYRA-300 0.625 mg/kg
Subsequent dose level escalations may occur based on criteria outlined in the protocol.
Sponsors
Tyra Biosciences, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 10 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Change from baseline in annualized growth velocity (Cohort 2) | 6 and 12 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 1) | 6 months |
| Change from baseline in height z-score (Cohort 2) | 6 and 12 months |
Countries
Australia, Canada, France, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTSuzanne Lopez
STUDY_CHAIRDoug Warner, MD
Tyra Biosciences
Outcome results
None listed