A Randomised, Multinational, Active-controlled, (Open-labelled), Dose Finding, (Double-blinded), Parallel Group Trial Investigating Efficacy and Safety of Once-weekly NNC0195-0092 Treatment Compared to Daily Growth Hormone Treatment (Norditropin® FlexPro®) in Growth Hormone Treatment naïve Pre-pubertal Children With Growth Hormone Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 126
- 主要终点
- Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer
研究概览
简要总结
This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency.
The main trial period will consist of 26 weeks of treatment, followed by a 26 week extension period.
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
- Double (Participant, Investigator)
盲法说明
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
入排标准
- 年龄范围
- 2 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Boys: Tanner stage 1 for pubic hair and testis volume below 4 ml , age at least 2 years and 26 weeks and below or equal to 10.0 years at screening
- •Girls: Tanner stage 1 for breast development (no palpable glandular breast tissue) and pubic hair, age at least 2 years and 26 weeks and below or equal to 9.0 years at screening
- •Confirmed diagnosis of GHD (growth hormone deficiency) within 12 months prior to screening as determined by two different GH (growth hormone) stimulation tests, defined as a peak GH level of below or equal to 7.0 ng/ml. For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed
- •No prior exposure to GH therapy and/or IGF-I (insulin-like growth factor I) treatment
- •Height of at least 2.0 standard deviations below the mean height for chronological age (CA) and gender according to the standards of Centers for Disease Control and Prevention 2-20 years: Girls/Boys stature-for-age and weight-for-age percentiles CDC at screening
- •Annualized height velocity (HV) below the 25th percentile for CA (chronological age) and gender or below -0.7 SD (standard deviation) score for CA and sex, according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months
排除标准
- •Any clinically significant abnormality likely to affect growth or the ability to evaluate
- •growth with standing measurements: Chromosomal aneuploidy and significant gene mutations causing medical "syndromes" with short stature, including but not limited to Turner syndrome, Laron syndrome, Noonan syndrome, or absence of GH receptors. Congenital abnormalities (causing skeletal abnormalities), including but not limited to Russell-Silver Syndrome, skeletal dysplasias. Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants
- •Children born small for gestational age (SGA - birth weight and/or birth length below-2 SD for gestational age)
- •Concomitant administration of other treatments that may have an effect on growth, including but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder (ADHD)
- •Prior history or presence of malignancy and/or intracranial tumour
研究组 & 干预措施
Cohort I Norditropin/somapacitan
Participants received Norditropin subcutaneously daily in main trial period, extension trial period and safety extension trial period. After completing the safety extension trial period (week 156), participants who received Norditropin were allocated to open-labelled Somapacitan dose 3 subcutaneously once weekly for the 208-week (up till week 364) long-term safety extension period. After week 364, participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.
干预措施: somapacitan (Drug)
Cohort I Norditropin/somapacitan
Participants received Norditropin subcutaneously daily in main trial period, extension trial period and safety extension trial period. After completing the safety extension trial period (week 156), participants who received Norditropin were allocated to open-labelled Somapacitan dose 3 subcutaneously once weekly for the 208-week (up till week 364) long-term safety extension period. After week 364, participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.
干预措施: Norditropin® FlexPro® pen (Drug)
Cohort I somapacitan pooled
Participants were randomized (1:1:1) to receive Somapacitan treatment (dose 1/dose 2/dose 3) subcutaneously once-weekly during the 26-week main trial period and the 26-week extension trial period. After completing the main and extension trial periods (week 52), all participants initially randomized to double-blinded Somapacitan received open-labelled Somapacitan dose 3 for the 104-week safety extension trial period. After completing the safety extension trial period (week 156), all participants in cohort I were allocated to open-labelled somapacitan dose 3 for the 208-week (up till week 364) long-term safety extension period. In extension after week 364 period participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.
干预措施: somapacitan (Drug)
Cohort II somapacitan previously treated
Participant who was previously treated with GH (Growth hormone) prior to enrollment in the trial at week 156, received somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.
干预措施: somapacitan (Drug)
Cohort III somapacitan treatment naive
Participants who were naive to treatment with GH prior to enrolment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.
干预措施: somapacitan (Drug)
Cohort III somapacitan previously treated
Participants who were previously treated with GH prior to enrollment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.
干预措施: somapacitan (Drug)
结局指标
主要结局
Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer
时间窗: Week 0-26
cm/year
Cohort II and III: Incidence of adverse events, including injection site reactions, in children with GHD
时间窗: During 208 weeks
Number of events
Height Velocity (HV) (cm/Year) During the First 26 Weeks of Treatment, Measured as Standing Height With Stadiometer
时间窗: Baseline (week 0), week 26
Height velocity (HV) was derived from height measurements taken at baseline (week 0) and the week 26 as: HV = (height at 26 weeks visit- height at baseline) / (time from baseline to 26 weeks visit in years).
Cohort II and Cohort III - Adverse Events Rate, Including Injection Site Reactions in Children With GHD.
时间窗: From week 156 up to week 364
This primary outcome measure was analysed by cohort using descriptive statistics. Adverse event per 100 patient years are presented in this outcome measure.
次要结局
- Insulin-like growth factor binding protein 3 (IGFBP-3) SDS(Week 26-52)
- Serum NNC0195-0092 (somapacitan) concentrations(Week 52)
- Changes in emotional well-being score, physical health score, social well-being score and total score in Treatment Related Impact Measure - Child Growth Hormone Deficiency- Observer (TRIM-CGHD-O)(Week 0-52)
- Change in height standard deviation score (SDS)(Week 26-52)
- Change in HV (height velocity) SDS(Week 0-52)
- Insulin-like growth factor 1 (IGF-I) SDS(Week 26-52)
- Height velocity(Week 52)
- Bone age(Week 52)
- Occurrence of anti-hGH antibodies(Week 364)
- Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O)(Week 52)
- Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P)(Week 52)
- Occurrence of anti-NNC0195-0092 (somapacitan) antibodies(Week 364)
- Cohort I: Change in Height Standard Deviation Score (HSDS)(Baseline (Week 0), week 26, week 52)
- Cohort I: Change in Height Velocity Standard Deviation Score (HVSDS)(Baseline (Week 0), week 26, week 52)
- Cohort I: Adverse Events Rate, Including Injection Site Reactions(From week 0 Up to week 364)
- Cohort I: Occurrence of Anti-NNC0195-0092 and Anti-hGH Antibodies(From week 0 Up to week 364)
- Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS)((Week 0), week 26, week 52)
- Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS)(Baseline (Week 0), week 26, week 52)
- Height Velocity (HV) (cm/Year) at Weeks 52 (Derived From Standing Height)(Baseline (week 0); week 52)
- Bone Age Progression vs. Chronological Age Ratio(At week 52)
- Serum Somapacitan Concentrations(At week 52)
- Changes in Emotional Well-being Score, Physical Health Score, Social Well-being Score and Total Score in TRIM-CGHD-O (Treatment Related Impact Measure - Child Growth Hormone Deficiency- Observer)(Baseline (Week 0), week 26, week 52)
- Total Score of TB-CGHD-O (The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer)(At week 26, at week 52)
- Total Score of TB-CGHD-P (The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian)(At week 26, at week 52)