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

Официальное название

A Multicenter, Phase 2, Dose-Escalation/Dose-Expansion Study of TYRA-300 in Children With Achondroplasia With Open Growth Plates: BEACH301

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат TYRA-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.
• Препарат TYRA-300 0.25 mg/kg
  Subsequent dose level escalations will occur based on criteria outlined in the protocol.
• Препарат TYRA-300 0.375 mg/kg
  Subsequent dose level escalations will occur based on criteria outlined in the protocol.
• Препарат TYRA-300 0.50 mg/kg
  Subsequent dose level escalations will occur based on criteria outlined in the protocol.

Первичные конечные точки

• Incidence of treatment-related adverse events as assessed by CTCAE v5.0 [Срок оценки: Up to 12 months]
• Change from baseline in annualized growth velocity (Cohort 1) [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Change from baseline in annualized growth velocity (Cohort 1) [Срок оценки: 6 months]
• Change from baseline in height z-score (Cohort 1) [Срок оценки: 6 and 12 months]
• Pharmacokinetics: maximum plasma concentration (Cmax) [Срок оценки: 15 days]
• Pharmacokinetics: time to reach maximum plasma concentration (Tmax) [Срок оценки: 15 days]
• Pharmacokinetics: area under the plasma concentration-time curve (AUC) [Срок оценки: 15 days]
• Pharmacokinetics: half-life of TYRA-300 (t1/2) [Срок оценки: 15 days]
• Pharmacokinetics: apparent total clearance (CL/F) [Срок оценки: 15 days]
• Pharmacokinetics: apparent volume of distribution (Vd/F) [Срок оценки: 15 days]
• Change from baseline in annualized growth velocity (Cohort 2) [Срок оценки: 6 and 12 months]
• Change from baseline in height z-score (Cohort 2) [Срок оценки: 6 and 12 months]
• Change from baseline in standing height (cm) [Срок оценки: 6 and 12 months]
• Change from baseline in sitting height (cm) [Срок оценки: 6 and 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• Lundquist Institute for Biomedical Innovation — Torrance
• Children's Hospital Colorado — Aurora
• Nemours Alfred I duPont Hospital for Children — Wilmington
• Johns Hopkins University School of Medicine — Baltimore
• Uncommon Cures — Chevy Chase
• University of Missouri — Columbia
• Washington University — St Louis
• Duke University Hospital — Durham
• … и ещё 4 центра

Канада · 3 центра

• Women's and Children's Health Research Institute, University of Alberta — Edmonton
• Children's Hospital of Eastern Ontario — Ottawa
• The Hospital for Sick Children — Toronto

Австралия · 2 центра

• The Children's Hospital at Westmead — Westmead
• Royal Children's Hospital — Parkville

Испания · 2 центра

• Unidad de Cirugía Artroscópica (MIKS Hospital) — Vitoria-Gasteiz
• Hospital Univeristario La Paz — Madrid

Великобритания · 2 центра

• Great Ormond Street Hospital — London
• Sheffield Children's Hospital — Sheffield

Франция · 1 центр

• Imagine Institute — Paris

Нидерланды · 1 центр

• UMC Utrecht — Utrecht

Швеция · 1 центр

• Astrid Lindgren Children's Hospital (Karolinska University Hospital) — Stockholm

Идентификаторы

NCT: NCT06842355 · TYR300-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗