NCT06164951已完成3 期
A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Infigratinib in Children 3 to <18 Years of Age With Achondroplasia: PROPEL 3
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 28
- 主要终点
- Change from baseline (BL) in annualized height velocity (cm/year)
研究概览
简要总结
This is a Phase 3, multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of infigratinib in children and adolescents with achondroplasia (ACH) who have completed at least 26 weeks of participation in the QED-sponsored study PROPEL (QBGJ398-001).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be 3 to <18 years of age at screening with growth potential defined as annualized height velocity of >1.5 cm/year over a period of at least 6 months of participation in the PROPEL observational study (QBGJ398-001), pubertal Tanner stage ≤4, and bone age ≤13 years in females and ≤15 years in males.
- •Type of Subject and Disease Characteristics
- •Subjects who have a diagnosis of ACH that has been documented clinically and confirmed by genetic testing.
- •Subjects must have completed at least 26 weeks in the PROPEL (QBGJ398-001) study before screening.
- •Subjects are able to swallow oral medication.
- •Subjects and parent(s), legal guardian(s), or caregivers are willing and able to comply with study visits and study procedures.
- •Subjects are ambulatory and able to stand without assistance.
- •Sex and Contraceptive/Barrier Requirements
- •Negative pregnancy test in girls ≥10 years of age or girls of any age who have experienced menarche.
- •If sexually active, subjects, whether male or female, must be willing to use a highly effective method of contraception while taking study drug and for 3 months after the last dose of study drug.
- •Informed Consent
- •Signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol, must be obtained for each subject from their parent(s) or legal guardian and signed informed consent/assent must be obtained from the subject (when applicable)
排除标准
- •Medical Conditions
- •Subjects who have hypochondroplasia or short stature condition other than ACH.
- •Significant concurrent disease or condition that, in the view of the investigator and/or sponsor, would confound assessment of efficacy or safety of infigratinib.
- •Current evidence of clinically significant corneal or retinal disorder/keratopathy -confirmed by ophthalmic examination.
- •Concurrent circumstance, disease or condition that, in the view of the investigator and/or sponsor, would interfere with study participation or safety evaluations and/or would require treatment with a prohibited medication, and/or would place the subject at high risk for poor treatment compliance or for not completing the study.
- •History and/or current evidence of extensive ectopic tissue calcification.
- •History of malignancy.
- •Prior/Concomitant Therapy
- •Having received or planning to receive treatment with any other investigational or approved product for the treatment of ACH or short stature.
- •Regular long-term treatment (≥3 weeks) with supraphysiologic doses of glucocorticoid therapy (ie, >15 mg/m2/day of hydrocortisone or equivalent) or treatment with glucocorticoids at anti-inflammatory doses (ie, 2.5-10 mg/kg/day of hydrocortisone or equivalent) for over 3 weeks within 6 months of the screening visit (low-dose local preparations including inhaled steroid for asthma, intranasal sprays for allergies, and topical steroids are allowed).
- •Previous limb-lengthening surgery at any time or planned/expected to have limb-lengthening surgery or guided growth surgery during the study period. Guided growth surgery with plates removed at least 12 months prior to screening is allowed.
- •Currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 or prolonged treatment (>1 week) with medications that alter the pH of the gastrointestinal tract including antacids, H2 antagonists (eg, ranitidine, famotidine), and proton-pump inhibitors (eg, omeprazole).
- •Current evidence of endocrine alterations of calcium/phosphorus homeostasis.
- •Diagnostic assessments
- •Subjects who have significant abnormality in screening laboratory results.
- •Other Exclusions
- •Having had a fracture of the long bones (ie, extremities) or spine within 12 months prior to screening.
- •Pregnant or breastfeeding at the screening visit or planning to become pregnant (self or partner) at any time during the study.
- •Allergy or hypersensitivity to any components of the study drug.
研究组 & 干预措施
Infigratinib 0.25 mg/kg/day
Experimental
Infigratinib at 2, 3.5, 5, 7, 10 mg
干预措施: Infigratinib 0.25 mg/kg/day (Drug)
Placebo 0.25 mg/kg/day
Placebo Comparator
Placebo Comparator at 2, 3.5, 5, 7, 10 mg
干预措施: Placebo Comparator 0.25 mg/kg/day (Drug)
结局指标
主要结局
Change from baseline (BL) in annualized height velocity (cm/year)
时间窗: Week 52
次要结局
- Change from BL in height Z-score (in relation to non-ACH tables)(Week 52)
- Absolute and change from baseline in arm span (cm) to standing height ratio(Week 52)
- Absolute and change from baseline in head circumference (cm) to standing height ratio(Week 52)
- Change in psychomotor function assessed by age-appropriate computerized tests (Detection Test), compared to placebo(Week 52)
- Annualized height velocity (cm/year)(Week 52)
- Absolute and change from baseline in upper leg to lower leg length ratio (cm)(Week 52)
- Change from BL in the Physical Functioning dimension of the Pediatric Quality of Life Generic Core Scale Short Form(Week 52)
- Change from BL in height Z-score (in relation to ACH tables)(Week 52)
- Change from BL in upper to lower body segment ratio(Week 52)
- Absolute value and change in body mass index(Week 52)
- Incidence of adverse events(Week 52)
- Change from BL in attention assessed by age-appropriate computerized tests (Identification Test)(Week 52)
- Absolute and change from baseline in upper arm to forearm length ratio (cm)(Week 52)
- Change from BL in annualized height velocity (cm/year) in children 5 years old and older, compared to placebo(Week 52)
- Change from BL in working memory assessed by age-appropriate computerized tests (One Back Test)(Week 52)
- Pharmacokinetic profile of infigratinib by assessment of maximum concentration (Cmax)(Week 52)
- Pharmacokinetic profile of infigratinib by assessment of time-to-maximum concentration (Tmax)(Week 52)
- Change from BL in collagen X marker concentration (ug/L)(Week 52)
- Change from BL in visual learning assessed by age-appropriate computerized tests (One Card Learning Test)(Week 52)
- Evaluate the acceptability and palatability of infigratinib using a 5-point hedonic scale(Week 13)
研究者
研究点 (28)
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