A Study to Evaluate the Safety and Tolerability of Multiple Ascending Doses of GS3-007a Dry Suspension in Patients With PGHD and to Evaluate the Efficacy and Safety of 52-week of Treatment With GS3-007a Dry Suspension: a Two-part, Multicenter, Randomized, Phase Ib/II Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 88
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a two-part clinical study for children with growth hormone deficiency. In the first part, participants will be randomly assigned to receive different doses of an oral treatment (GS3-007a dry suspension) or a placebo for 14 days. This part is double-blinded, meaning neither the participants nor the doctors will know who is receiving the treatment or placebo. The goal is to find a safe and well-tolerated dose.
In the second part, participants will be randomly assigned to receive either the selected dose of GS3-007a or another approved treatment for 52 weeks. This part is open-label, so everyone will know which treatment is being given. After that, all participants may continue taking GS3-007a for another 156 weeks in an extension phase to study long-term effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •chronological age (CA) ≥3 years at Screening
- •Prepubertal girls or boys
- •Height at Screening lower than the reference height for normal children of the same chronological age and sex minus 2 standard deviations (-2 SD)
- •A confirmed diagnosis of growth hormone deficiency (GHD)
- •Having not been treated with any growth-promoting drugs
- •BA delayed by ≥6 months compared with the CA at Screening Subjects who meet all of the following criteria are eligible to enroll in the extension study (applicable for Part II extension period)
- •Subjects who have completed the 52-week treatment period of phase II
- •Subjects who do not permanently discontinue the investigational Medicinal Product (IMP) during the 52-week treatment period of phase II
排除标准
- •A highly allergic constitution
- •Suspected or confirmed total pituitary deficiency, including patients previously confirmed with deficiency of ≥2 pituitary hormones other than GH
- •Being confirmed with other chromosomal abnormalities or growth abnormalities affecting growth
- •Congenital skeletal dysplasia or serious spinal anomalies
- •Cognitive hypofunction, neurodevelopmental disorders, or psychiatric/psychological disorders that, in the investigator's opinion, may interfere with evaluation of study endpoints
- •Any clinically significant abnormality that may affect growth or evaluation of the IMP
- •Screening magnetic resonance imaging (MRI) scan of the sellar region confirming prior or current intracranial tumor growth
- •Concurrent use of any medications that may affect growth or response to growth hormone therapy
- •Epiphyseal closure
- •Electrocardiogram (ECG) QTcF interval abnormal, with a history of QT/QTc interval prolonged
- •Hepatic function indicators abnormal at Screening Patients meeting any of the following criteria may not be enrolled in this extension study (applicable for Part II extension period)
- •Subjects with closed epiphyses
- •Any clinically significant abnormality that may affect growth or evaluation of the IMP
- •Known or suspected allergy to the IMP
- •Women with positive blood human chorionic gonadotropin (hCG) at the pre-treatment visit
研究组 & 干预措施
Dose Level 1~ Dose Level 4
dose level 1、dose level 2、dose level 3、dose level 4
干预措施: Placebo for GS3-007a dry suspension (Drug)
Cohort 1~ Cohort 3
GS3-007a low dose , GS3-007a high dose , rhGH 0.033mg/kg
干预措施: GS3-007a dry suspension (Drug)
Cohort 1~ Cohort 3
GS3-007a low dose , GS3-007a high dose , rhGH 0.033mg/kg
干预措施: rhGH injection (Drug)
GS3-007a cohort
GS3-007a optimal dose
干预措施: GS3-007a dry suspension (Drug)
Dose Level 1~ Dose Level 4
dose level 1、dose level 2、dose level 3、dose level 4
干预措施: GS3-007a dry suspension (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: up to 21 days (Ib phase)
Annualized height velocity (AHV) at Week 26 of treatment
时间窗: 26 weeks (II phase)
Number of Participants With TEAEs
时间窗: up to 160 weeks (II phase extension)
次要结局
- Plasma Concentrations of GS3-007a and metabolite GS3-017. Due to Spare sampling time, there are no PK parameter(up to 7 days (Ib phase))
- AHVs at each evaluation point(13 weeks, 39 weeks, 52 weeks (II phase))
- The standard deviation score (SDS) for an individual IGF-I measurement is calculated using the age-specific L, M, and S parameters, no minimum and maximum values, with higher scores indicating treatment improvement in PGHD(4 weeks, 13 weeks, 26 weeks, 39 weeks, 52 weeks (II phase))
- The standard deviation score (SDS) for an individual height measurement is calculated using the age-specific L, M, and S parameters, no minimum and maximum values, with higher scores indicating treatment improvement in PGHD(up to 156 weeks (II phase extension))
- PK concentrations of GS3-007a and metabolite GS3-017(up to 7 days (Ib phase))
- Concentrations of serum growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3)(up to 14 days (Ib phase))
- AHVs at each evaluation point(up to 156 weeks (II phase extension))
- Changes from baseline (ΔIGF-1 SDS) in the standard deviation score of the PD indicator insulin-like growth factor-1 (IGF-1 SDS) at each evaluation point(4 weeks, 13 weeks, 26 weeks, 39 weeks, 52 weeks (II phase))
- Change from extension baseline in the height standard deviation score at each evaluation point (ΔHT SDS)(up to 156 weeks (II phase extension))