A Research Study in Chinese Children With a Low Level of Hormone to Grow. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day.

Phase 3

Completed

Conditions: Growth Hormone Deficiency in Children

Interventions: Drug: Norditropin®
Drug: somapacitan

Registration Number: NCT04970654

Lead Sponsor: Novo Nordisk A/S

Brief Summary: The study compares two medicines for children with a low level of hormone to grow: somapacitan (a new medicine) given once a week and Norditropin® (a medicine doctors can already prescribe) given once a day. Researchers will test somapacitan to see how well it works, compared to the standard treatment with Norditropin®. The participants will either get Norditropin® once every day or somapacitan once every week - which treatment the participant gets is decided by chance. The participant and the study doctor will know which treatment the participant gets. The study includes a 52 week treatment period and a minimum of 30 days follow up period.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 110

Inclusion Criteria

Informed consent of parent or legally acceptable representative of participant and child assent, as age-appropriate must be obtained before any trial related activities
The parent or legally acceptable representative of the child must sign and date the Informed consent form (according to local requirements)
The child must sign and date child assent form or provide oral assent (if required according to local requirements)
Prepubertal children: a) Boys: Age more than or equal to 2 years and 26 weeks and less than or equal to 11.0 years at the time of signing informed consent.
Testis volume less than 4 ml. b) Girls: Age more than or equal to 2 years and 26 weeks and less than or equal to 10.0 years at the time of signing informed consent. Tanner stage 1 for breast development (no palpable glandular breast tissue)
Confirmed diagnosis of growth hormone deficiency determined by two different growth hormone stimulation tests performed within 12 months prior to randomisation, defined as a peak growth hormone level of less than or equal to 10.0 ng/ml using the WHO International Somatropin 98/574 standard
If only one growth hormone stimulation test is available before screening, then confirmation of growth hormone deficiency by second and different growth hormone stimulation test must be done
For children with at least 2 additional pituitary hormone deficiencies (other than growth hormone deficiency) only one growth hormone stimulation test is needed
Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender according to Chinese general population standards at screening
Impaired height velocity defined as annualised height velocity at screening less than 7cm/year for subjects between 2.5 and 3 years old and less than 5 cm/year for subjects from 3 years and above calculated over a time span of minimum 3 months and maximum 18 months prior to screening according to Chinese guideline and expert consensus on children with short stature and GH therapy
No prior exposure to growth hormone therapy or IGF-I treatment
Bone age less than chronological age at screening
Body Mass Index more than 5th and less than 95th percentile, Body Mass Index-for-age growth charts according to Chinese general population standards.
IGF-I < -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory
No intracranial tumour confirmed by magnetic resonance imaging or computer tomography scan. An image or scan taken within 9 months prior to screening can be used as screening data if the medical evaluation and conclusion is available

Exclusion Criteria

Known or suspected hypersensitivity to trial product(s) or related products.
Previous participation in this trial. Participation is defined as randomisation.
Receipt of any investigational medicinal product within 3 months before screening or participation in another clinical trial before randomisation
Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements:
Turner Syndrome (including mosaicisms)
Chromosomal aneuploidy and significant gene mutations causing medical "syndromes" with short stature, including but not limited to Laron syndrome, Noonan syndrome, Prader-Willi Syndrome, abnormal SHOX-1 gene analysis or absence of GH receptors
Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants
Congenital abnormalities (causing skeletal abnormalities), including but not limited to Russell-Silver Syndrome or skeletal dysplasias
Family history of skeletal dysplasia
Children born small for gestational age (birth weight 10th percentile of the recommended gender-specific birth weight for gestational age according to national standards in China5
Children diagnosed with diabetes mellitus or screening values from central laboratory of
1. fasting plasma glucose more than or equal to 126 mg/dl (7.0 mmol/L) or
2. HbA1c more than 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 µg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening
Concomitant administration of other treatments that may have an effect on growth, e.g. but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder (ADHD)
Diagnosis of attention deficit hyperactivity disorder
Prior history or presence of malignancy including intracranial tumours
Prior history or known presence of active Hepatitis B or Hepatitis C (exceptions to this exclusion criterion is the presence of antibodies due to vaccination against Hepatitis B)
Any clinically significant abnormal laboratory screening tests, as judged by the study doctor
Any disorder which, in the opinion of the study doctor, might jeopardise Participant's safety or compliance with the protocol
The participant or the parent/legally acceptable representative is likely to be non-compliant in respect to trial conduct, as judged by the study doctor
Children with hypothyroidism and/or adrenal insufficiency not on adequate and stable replacement therapy for at least 90 days prior to randomisation.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Norditropin® daily	Norditropin®	Participants will receive Norditropin® daily for 52 weeks
Somapacitan weekly	somapacitan	participants will receive once-weekly somapacitan for 52 weeks

Primary Outcome Measures

Name	Time	Method
Height Velocity	Baseline (Week 0); Week 52	Height velocity (HV) was derived from height measurements taken at baseline (week 0) and the week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years).

Secondary Outcome Measures

Name	Time	Method
Change in Bone Age	Week -2, week 52	Change in bone age is presented from week -2 to week 52. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in Height Standard Deviation Score	Baseline (week 0), week 52	Change in the height standard deviation score (HSDS) is presented from baseline (week 0) to week 52. HSDS was derived using Chinese general population standards. The formula to calculate HSDS is: HSDS = ((Height / M)\\L-1) / (L\*S). L: The sex and age-specific power in the Box-Cox transformation, M: The sex and age-specific median, S: The sex and age-specific generalized coefficient of variation. The range for HSDS was -10 to +10. Negative scores indicated a height below the mean height for a child with the same age and gender, whereas positive scores indicated a height above the mean height for a child with the same age and gender. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in Height Velocity Standard Deviation Score	Baseline (week 0), week 52	Change in height velocity standard deviation score (HVSDS) is presented from baseline (week 0) to week 52. HVSDS was derived using Prader standards. HVSDS was calculated using the formula: HVSDS = (height velocity - mean)/standard deviation (SD), where height velocity was the height velocity variable measured, mean and SD of height velocity by gender and age for the reference population. The range for HVSDS was -10 to +10. Negative scores indicated a height velocity below the mean height velocity for a child with the same age and gender, whereas positive scores indicated a height velocity above the mean height velocity for a child with the same age and gender. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in Fasting Plasma Glucose	Baseline (week 0), week 52	Change in fasting plasma glucose is presented from baseline (week 0) to week 52. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in HbA1c	Baseline (week 0), week 52	Change in glycosylated haemoglobin (HbA1c) is presented from baseline (week 0) to week 52 is presented. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in IGF-I Standard Deviation Score	Baseline (week 0), week 52	Change in Insulin like growth factor-I (IGF-I) standard deviation score is presented from baseline (week 0) to week 52. The range for IGF-I SDS was from -10 to +10. Negative scores indicated a IGF-I below the mean IGF-I for a child with the same age and gender, whereas positive scores indicated a IGF-I above the mean IGF-I for a child with the same age and gender. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.
Change in IGFBP-3 Standard Deviation Score	Baseline (week 0), week 52	Change in Insulin like growth factor binding protein 3 (IGFBP-3) standard deviation score is presented from baseline (week 0) to week 52. The range for IGFBP-3 SDS was from -10 to +10. Negative scores indicated a IGFBP-3 below the mean IGFBP-3 for a child with the same age and gender, whereas positive scores indicated a IGFBP-3 above the mean IGFBP-3 for a child with the same age and gender. This outcome measure was analysed based on the 'on treatment' observation period. On treatment observation period: It starts from first administration of trial product and up until last trial contact, visit 7 (52 weeks+5 days) or 14 days after last administration, whichever comes first.

Trial Locations

Locations (20): Hunan Children's Hospital
🇨🇳
Changsha, Hunan, China
Jiangxi Provincial Children's Hospital
🇨🇳
Nanchang, Jiangxi, China
The Second Hospital of Anhui Medical University
🇨🇳
Hefei, Anhui, China
Capital Institute of Paediatrics
🇨🇳
Beijing, Beijing, China
Tongji Hospital，Tongji Medical College of Huazhong University of Science &Technology
🇨🇳
Wuhan, Hubei, China
The First Affiliated Hospital of Shaoyang University
🇨🇳
Shaoyang, Hunan, China
Children's Hospital of Soochow University
🇨🇳
Suzhou, Jiangsu, China
Pingxiang Maternal and Child Health Care Hospital
🇨🇳
Pingxiang, Jiangxi, China
Qingdao Women and Children's Hospital
🇨🇳
Qingdao, Shandong, China
Henan Children's Hospital
🇨🇳
Zhengzhou, Henan, China
Beijing Children's Hospital，Capital Medical University
🇨🇳
Beijing, Beijing, China
The First Affiliated Hospital , Sun Yat-sen University
🇨🇳
Guangzhou, Guangdong, China
Henan Children's Hospital Zhengzhou Children's Hospital
🇨🇳
Zhengzhou, Henan, China
The Second Xiangya Hospital of Central South University
🇨🇳
Changsha, Hunan, China
Wuxi Children's Hospital
🇨🇳
Wuxi, Jiangsu, China
The First Hospital of Jiaxing
🇨🇳
Jiaxing, Jiangxi, China
The First Hospital of Jilin University
🇨🇳
Changchun, Jilin, China
Shandong Provincial Hospital
🇨🇳
Jinan, Shandong, China
Chengdu Women's and Children's central hospital
🇨🇳
Chengdu, Sichuan, China
The Children's Hospital, Zhejiang University school of medicine
🇨🇳
Hangzhou, Zhejiang, China