A Study Evaluating the Safety and Efficacy of Once-weekly Dosing of Somapacitan in a Basket Study Design in Paediatric Participants With Short Stature Either Born Small for Gestational Age or With Turner Syndrome, Noonan Syndrome or Idiopathic Short Stature
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 47
- 试验地点
- 25
- 主要终点
- Number of Adverse Events (AEs) Reported in Children Born Small for Gestational Age- Weeks 0 to 26
研究概览
简要总结
The purpose of this study is to find out if somapacitan is safe and how well somapacitan works in children either born small for gestational age or with Turner syndrome, Noonan syndrome or idiopathic short stature. Somapacitan is a new growth hormone medicine for treatment of low level of growth hormone. The study will last for about 3 years. During the study, the participants will be treated with somapacitan once a week. Somapacitan can be injected anytime during the day. The study doctor or nurse will show how to inject somapacitan, so that the participant knows how to do it at home.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Applicable to children with SGA:
- •Born small for gestational age (birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
- •- Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.
- •- Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.
- •Open epiphyses; defined as bone age less than (<) 14 years for females and bone age < 16 years for males.
- •For Growth Hormone (GH) treatment naïve participants: Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
- •Applicable to children with TS:
- •Diagnosis of TS according to local clinical practice.
- •- Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.
- •Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
- •For GH treatment naïve participants: Impaired height defined as at least 2.0 standard deviation below the mean height for chronological age and sex at screening according to the standards of Centers for Disease Control and Prevention.
- •For GH treatment naïve participants: Confirmed diagnosis of TS by 30-cell (or more) lymphocyte chromosomal analysis or confirmation of TS and TS mosaicism using comparative genomic hybridization (CGH)-array.
- •Applicable to children with NS:
- •Diagnosis of NS according to local clinical practice.
- •Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.
- •Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.
- •Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
- •For GH treatment naïve participants: Clinical diagnosis of NS according to van der Burgt score list and genetic test result or confirmed mutation in any of the genes associated with NS before allocation.
- •Applicable to children with ISS:
- •- Male participants: Age equal to or above 11.0 years and below 18.0 years at screening.
- •- Female participants: Age equal to or above 10.0 years and below 18.0 years at screening.
- •Open epiphyses; defined as bone age < 14 years for females and bone age < 16 years for males.
- •For GH treatment naïve participants: Impaired height defined as at least 2.5 standard deviations below the mean height for chronological age and sex at screening
- •For GH treatment naïve participants: Normal GH secretion (GH peak above 7 ng/mL) during GH stimulation test performed within 18 months prior to screening.
- •For GH treatment naïve participants: Bone age not delayed more than 2 years compared to chronological age at screening.
排除标准
- •Children with suspected or confirmed growth hormone deficiency according to local practice.
- •Children diagnosed with diabetes mellitus or screening values from the central laboratory.
- •Fasting plasma glucose above or equal to 126 milligrams per deciliter (mg/dL) [7.0 millimoles per litre (mmol/L)] or
- •Glycated hemoglobin (HbA1c) above or equal to 6.5%.
- •Current inflammatory diseases requiring systemic corticosteroid treatment for longer than 2 consecutive weeks within the last 3 months prior to screening.
- •Children requiring inhaled glucocorticoid therapy at a dose greater than 400 micrograms per day (µg/day) of inhaled budesonide or equivalent (i.e., 250 µg/day for fluticasone propionate) for longer than 4 consecutive weeks within the last 12 months prior to screening.
- •History or known presence of malignancy including intracranial tumours.
- •Applicable to children with SGA:
- •Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:
- •Poorly controlled or uncontrolled hormonal deficiencies.
- •Known chromosomal aneuploidy or significant gene mutations causing medical 'syndromes' with short stature, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, skeletal dysplasias, abnormal short stature homeobox (SHOX) gene analysis or absence of GH receptors.
- •Applicable to children with TS:
- •Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:
- •Known family history of skeletal dysplasia.
- •Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
- •Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
- •Mosaicism below 10%.
- •TS with Y-chromosome mosaicism where gonadectomy has not been performed.
- •New York Heart Association (NYHA) class II or above or requiring medication for any heart condition.
- •Applicable to children with NS:
- •Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:
- •Known family history of skeletal dysplasia.
- •Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
- •Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
- •Noonan-related disorders including but not limited to: Noonan syndrome with multiple lentigines (formerly called 'LEOPARD' syndrome), Noonan syndrome with loose anagen hair, cardiofaciocutaneous syndrome (CFC), Costello syndrome, neurofibromatosis type 1 (NF1) and Legius syndrome.
- •Applicable to children with ISS:
- •Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with height, such as, but not limited to:
- •Known family history of skeletal dysplasia.
- •Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
- •Any other disorder that can cause short stature such as, but not limited to nutritional disorders, chronic systemic illness and chronic renal disease.
- •Poorly controlled or uncontrolled hormonal deficiencies.
- •Known chromosomal aneuploidy or significant gene mutations causing medical 'syndromes' with short stature, including but not limited to Laron syndrome, Prader-Willi syndrome, Russell-Silver Syndrome, skeletal dysplasias, abnormal SHOX gene analysis or absence of GH receptors.
研究组 & 干预措施
Somapacitan
Participants will receive Somapacitan for 26-week main phase followed by 130-week extension phase.
干预措施: Somapacitan (Drug)
结局指标
主要结局
Number of Adverse Events (AEs) Reported in Children Born Small for Gestational Age- Weeks 0 to 26
时间窗: From baseline (Week 0) to Week 26
This outcome measure reported number of AEs in children with short stature for indication SGA. Children with SGA are born small for gestational age with insufficient catch-up growth by 2 years of age or older. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an study treatment.
Number of Adverse Events Reported for Turner Syndrome (TS)- Weeks 0 to 26
时间窗: From baseline (Week 0) to Week 26
This outcome measure reported number of AEs in participants with short stature for indication TS. TS is a chromosomal disorder which leads to short stature. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an study treatment.
Number of Adverse Events Reported for Noonan Syndrome- Weeks 0 to 26
时间窗: From baseline (Week 0) to Week 26
This outcome measure reported number of AEs in participants with short stature for indication NS which is a genetically heterogeneous developmental disorder characterized by postnatally reduced growth and other major disorders. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an study treatment.
Number of Adverse Events Reported for Idiopathic Short Stature (ISS)- Weeks 0 to 26
时间窗: From baseline (Week 0) to Week 26
This outcome measure reported number of AEs in participants with short stature for indication ISS. ISS describes short children with normal GH secretion. ISS is a condition in which the height of the individual is more than 2 standard deviations below the corresponding mean height for a given age, sex and population, without evidence of systemic, endocrine, nutritional or chromosomal abnormalities. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of an study treatment.
次要结局
- Number of Adverse Events Possibly or Probably Related to Somapacitan Reported for Children Born Small for Gestational Age(From baseline (Week 0) to Week 26)
- Number of Adverse Events Possibly or Probably Related to Somapacitan Reported for Turner Syndrome(From baseline (Week 0) to Week 26)
- Number of Adverse Events Possibly or Probably Related to Somapacitan Reported for Noonan Syndrome(From baseline (Week 0) to Week 26)
- Number of Adverse Events Possibly or Probably Related to Somapacitan Reported for Idiopathic Short Stature(From baseline (Week 0) to Week 26)
- Number of Adverse Events Reported Long-term Safety for Children Born Small for Gestational Age- Weeks 0 to 156(From baseline (Week 0) to Week 156)
- Number of Adverse Events Reported Long-term Safety for Turner Syndrome- Weeks 0 to 156(From baseline (Week 0) to Week 156)
- Number of Adverse Events Reported Long-term Safety for Noonan Syndrome- Weeks 0 to 156(From baseline (Week 0) to Week 156)
- Number of Adverse Events Reported Long-term Safety for Idiopathic Short Stature- Weeks 0 to 156(From baseline (Week 0) to Week 156)
- Height Velocity Reported Children Born Small for Gestational Age(From Baseline (Week 0) to Week 26)
- Height Velocity Reported for Turner Syndrome(From Baseline (Week 0) to Week 26)
- Height Velocity Reported for Noonan Syndrome(From Baseline (Week 0) to Week 26)
- Height Velocity Reported for Idiopathic Short Stature(From Baseline (Week 0) to Week 26)
- Change in Height Standard Deviation Scores (SDS) Reported for Children Born Small for Gestational Age(Baseline (Week 0), Week 26)
- Change in Height Standard Deviation Scores Reported for Turner Syndrome(Baseline (Week 0), Week 26)
- Change in Height Standard Deviation Scores Reported for Noonan Syndrome(Baseline (Week 0), Week 26)
- Change in Height Standard Deviation Scores Reported for Idiopathic Short Stature(Baseline (Week 0), Week 26)
- Change in Height Velocity Standard Deviation Scores Reported Separately for Children Born Small for Gestational Age(Baseline (Week 0), Week 26)
- Change in Height Velocity Standard Deviation Scores Reported Separately for Turner Syndrome(Baseline (Week 0), Week 26)
- Change in Height Velocity Standard Deviation Scores Reported for Noonan Syndrome(Baseline (Week 0), Week 26)
- Change in Height Velocity Standard Deviation Scores Reported Separately for Idiopathic Short Stature(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor 1 (IGF-1) Standard Deviation Score Reported for Children Born Small for Gestational Age(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor 1 Standard Deviation Score Reported for Turner Syndrome(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor 1 Standard Deviation Score Reported for Noonan Syndrome(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor 1 Standard Deviation Score Reported Separately for Idiopathic Short Stature(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) SDS Reported for Children Born Small for Gestational Age(Baseline (week 0), Week 26)
- Change in Insulin-like Growth Factor Binding Protein-3 SDS Reported for Turner Syndrome(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor Binding Protein-3 SDS Reported for Noonan Syndrome(Baseline (Week 0), Week 26)
- Change in Insulin-like Growth Factor Binding Protein-3 SDS Reported for Idiopathic Short Stature(Baseline (Week 0), Week 26)
- Weekly Average Somapacitan Concentration (Cavg) Reported for Children Born Small for Gestational Age(Weeks 4, 8, 13, 20 and 26)
- Weekly Average Somapacitan Concentration (Cavg) Reported for Turner Syndrome(Weeks 4, 8, 13, 20 and 26)
- Weekly Average Somapacitan Concentration (Cavg) Reported for Noonan Syndrome(Weeks 4, 8, 13, 20 and 26)
- Weekly Average Somapacitan Concentration (Cavg) Reported for Idiopathic Short Stature(Weeks 4, 8, 13, 20 and 26)