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.

Study Overview
=================
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.

Official Title
-----------------
A Trial Comparing the Efficacy and Safety of Once Weekly Dosing of Somapacitan With Daily Norditropin® in Chinese Children With Growth Hormone Deficiency

Conditions
-----------------
Growth Hormone Deficiency in Children

Intervention / Treatment
-----------------
* Drug: somapacitan
* Drug: Norditropin®


Participation Criteria
=================
Eligibility Criteria
-----------------
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 fasting plasma glucose more than or equal to 126 mg/dl (7.0 mmol/L) or 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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somapacitan weekly<br>participants will receive once-weekly somapacitan for 52 weeks | Drug: somapacitan<br>* Somapacitan (0.16 mg/kg/week) will be administered subcutaneously (s.c.; under the skin) once weekly by PDS290 pen-injector. Somapacitan can be injected any time during the once weekly dosing day. The dose will be calculated based on the subject's current body weight.<br>|
| Active Comparator: Norditropin® daily<br>Participants will receive Norditropin® daily for 52 weeks | Drug: Norditropin®<br>* Norditropin® (0.034 mg/kg/day) will be administered s.c. once daily by FlexPro® pen-injector. Norditropin® should be injected daily in the evening. The dose will be calculated based on the subject's current body weight.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height velocity | Height velocity (HV) is measured in cm/year. HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). | week 0 - 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in height Standard Deviation Score (SDS) | Measured in scores (-10 to +10). Height SDS will be derived using Centre for Disease Control and Prevention (CDC) standards. | from baseline (week 0) to week 52 | 
| Change in height Velocity Standard Deviation Score | Measured in scores (-10 to +10). HV SDS will be derived using Prader standards as reference data. | from baseline (week 0) to week 52 | 
| Change in bone age | Measured in years | from Visit 1 to Week 52 | 
| Change in fasting plasma glucose | Measured in mmol/L. | from baseline (week 0) to week 52 | 
| Change in glycated haemoglobin (HbA1c) | Measured in percentage | from baseline (week 0) to week 52 | 
| Change in IGF-I Standard Deviation Score | Measured in scores (-10 to +10) | From baseline (week 0) to week 52 | 
| Change in IGFBP-3 Standard Deviation Score | Measured in scores (-10 to +10) | From baseline (week 0) to week 52 |