A Phase 2, Randomized, Controlled, Multicenter Study of Vosoritide in Children With Idiopathic Short Stature
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 47
- 主要终点
- Change from baseline in Annualized Growth Velocity (AGV)
研究概览
简要总结
The purpose of this study is to evaluate i) the effect of multiple doses of vosoritide and ii) the effect of the therapeutic dose of vosoritide compared to human growth hormone (hGH)(hGH; only in the United States), in children with idiopathic short stature (ISS).
详细描述
Following a minimum 6 month observational period in which baseline growth is assessed, participants in the vosoritide and placebo groups will complete a minimum of 6 months of randomized treatment (maximum of 6 months of placebo treatment), followed by open-label treatment with vosoritide until they reach near-final adult height, or at least 16 years of age for females or 18 years of age for males, whichever comes later. Participants randomized to the hGH group will receive open-label hGH for a minimum of 4 years.
A Treatment Completion visit will occur approximately 4 weeks after the last administration of investigational product. Participants who discontinue study treatment after ≥13 weeks of exposure may remain in the study and complete follow-up assessments per the protocol schedule (including annual and periodic assessments through End of Study). If a participant discontinues treatment and declines further participation, they will be asked to return for a final Treatment Completion and End of Study visit approximately 4 weeks after the last injection.
Safety monitoring includes regular clinical and imaging assessments, including hip and lower-extremity evaluations, monitoring for hypotension, fractures, and slipped capital femoral epiphysis, with oversight by an independent Data Monitoring Committee
An independent Data Monitoring Committee will periodically review safety data and may recommend treatment discontinuation based on predefined safety signals
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 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth charts
- •If participant is ≥ 5 years at Screening,must be Tanner Stage I to be eligible for enrollment and randomization
- •Historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (≥ -1.00 SDs and ≤+2.00 SDs).
- •Key Exclusions:
- •Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome), ACAN deficiency.
- •Previous treatment with a growth promoting agent
排除标准
- •Known chromosomal imbalance or genetic variant causing short stature syndrome, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, Turner syndrome, disproportionate skeletal dysplasias, abnormal SHOX gene analysis, or Rasopathy (including Noonan syndrome)
- •Previous treatment with a growth promoting agent
研究组 & 干预措施
Placebo
Placebo daily injection
干预措施: Placebo (Drug)
Vosoritide Dose 2 - Medium Dose
Vosoritide Dose 2 daily injection
干预措施: Vosoritide Injection (Drug)
Vosoritide Dose 3 - High Dose
Vosoritide Dose 3 daily injection
干预措施: Vosoritide Injection (Drug)
Human Growth Hormone
hGH daily injection (US only)
干预措施: Human Growth Hormone (Drug)
Vosoritide Dose 1 - Low Dose
Vosoritide Dose 1 daily injection
干预措施: Vosoritide Injection (Drug)
结局指标
主要结局
Change from baseline in Annualized Growth Velocity (AGV)
时间窗: At 6 months
Change from baseline in height
时间窗: At 4 years
Change from baseline in height Z-score
时间窗: At 4 years
次要结局
- Change from baseline at pre-specified timepoints in serum collagen X marker (CXM)(Every 6 months through the end of study, up to 15 years)
- Change from baseline in bone age minus chronological age at pre-specified timepoints(Every 6 months through the end of study, up to 15 years)
- Change from baseline in total body (less head) bone mineral density (BMD) Z-score(Every 6 months through the end of study, up to 15 years)
- Incidence of treatment-emergent adverse events(Until the end of the study, up to 15 years)
- Change from baseline in Height Z-score (average stature reference)(At 6 months)
- Change from baseline in height(Every 6 months through the end of study, up to 15 years)
- Change from baseline in height Z score(Every 6 months through the end of study, up to 15 years)
- Maximum concentration (Cmax) of vosoritide in plasma(Every 6 months through the end of study, up to 15 years)
- Change from baseline at prespecified timepoints in urine cyclic guanine monophosphate (cGMP)(Every 6 months through the end of study, up to 15 years)
- Change from baseline in lumbar spine BMD Z-score(Every 6 months through the end of study, up to 15 years)
- Area under the plasma vosoritide concentration time-curve from time 0 to infinity (AUC0-∞)(Every 6 months through the end of study, up to 15 years)
- Change from baseline in total body (less head) bone mineral content (BMC)(Every 6 months through the end of study, up to 15 years)
- Change from baseline in lumbar spine BMC(Every 6 months through the end of study, up to 15 years)
- Area under the plasma vosoritide concentration time-curve from time 0 to the last measurable concentration (AUC0-t)(Every 6 months through the end of study, up to 15 years)
- Elimination half-life of vosoritide (t½)(Every 6 months through the end of study, up to 15 years)
- Apparent clearance of vosoritide(Every 6 months through the end of study, up to 15 years)
- Apparent volume of distribution of vosoritide based upon the terminal phase (Vz/F)(Every 6 months through the end of study, up to 15 years)
- Time vosoritide is present at maximum concentration (Tmax)(Every 6 months through the end of study, up to 15 years)
研究者
BioMarin Pharmaceutical Inc.
Scientific
Biomarin Pharmaceutical Inc.