A Multicenter, Phase 2, Dose-Escalation/Dose-Expansion Study of TYRA-300 in Children With Achondroplasia With Open Growth Plates: BEACH301
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 30
- 主要终点
- Incidence of treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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) 3A
- •History or current evidence of corneal or retinal disorder/keratopathy.
- •Presence of guided growth hardware/8 plates. Planned or anticipated orthopedic surgeries.
研究组 & 干预措施
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.
干预措施: TYRA-300 0.125 mg/kg (Drug)
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.
干预措施: TYRA-300 0.375 mg/kg (Drug)
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.
干预措施: TYRA-300 0.50 mg/kg (Drug)
TYRA-300 0.625 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.
干预措施: TYRA-300 0.625 mg/kg (Drug)
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.
干预措施: TYRA-300 0.25 mg/kg (Drug)
结局指标
主要结局
Incidence of treatment-related adverse events as assessed by CTCAE v5.0
时间窗: Up to 12 months
Change from baseline in annualized growth velocity (Cohort 1)
时间窗: 12 months
次要结局
- 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 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 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)