A Research Study in Children With a Low Level of Hormone to Grow. Treatment is Somapacitan Once a Week Compared to Norditropin® Once a Day (REAL4)

Study Overview
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Brief Summary
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The study compares 2 medicines for children who do not have enough hormone to grow: somapacitan given once a week (a new medicine) and Norditropin® given once a day (the medicine doctors can already prescribe). Researchers will test to see how well somapacitan works. The study will also test if somapacitan is safe. Participants will either get somapacitan or Norditropin® - which treatment participants get, is decided by chance. Both participants and the study doctor will know which treatment participants get. The study will last for 4 years. Participants will attend 19 clinic visits and have 1 phone call with the study doctor.

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

Conditions
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Growth Hormone Deficiency in Children

Intervention / Treatment
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* Drug: Somapacitan
* Drug: Norditropin®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prepubertal children: a) Boys: Age more than or equal to 2 years and 26 weeks and less than 11.0 years at screening. Testis volume less than 4 ml. b) Girls: Age more than or equal to 2 years and 26 weeks and less than 10.0 years at screening. 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 World Health Organisation (WHO) International Somatropin 98/574 standard Impaired height defined as at least 2.0 standard deviations below the mean height for chronological age and gender at screening according to the standards of Center for Disease Control and Prevention Impaired height velocity, defined as annualised height velocity below the 25th percentile for chronological age and gender according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months prior to screening Insulin-like Growth Factor-I (IGF-I) less than -1.0 SDS at screening, compared to age and gender normalized range measured at central laboratory No prior exposure to growth hormone therapy or IGF-I treatment Exclusion Criteria: Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements 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 of greater than 400 μg/day of inhaled budesonide or equivalents for longer than 4 consecutive weeks within the last 12 months prior to screening Diagnosis of attention deficit hyperactivity disorder 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 Prior history or presence of malignancy including intracranial tumours

Ages Eligible for Study
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Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will receive either somapacitan once weekly or Norditropin® once daily for 52 weeks (main trial period). All participants completing the main trial period will receive somapacitan weekly for 3 years (extension trial period).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somapacitan weekly<br>Participants will receive somapacitan weekly for 52 weeks (main trial period). Participants completing the main trial period in both the treatment arms ('Somapacitan weekly' and 'Norditropin® daily') will receive somapacitan weekly for 3 years (extension trial period). | Drug: Somapacitan<br>* Somapacitan 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 (main trial period). | Drug: Norditropin®<br>* Norditropin® 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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity: In-trial Observation Period | Height velocity (HV) was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | From baseline (week 0) to visit 7 (week 52) | 
| Height Velocity: On-treatment Observation Period | Height velocity was derived from height measurements taken at baseline and Week 52 visit as: HV = (height at 52 weeks visit - height at baseline)/(time from baseline to 52 weeks visit in years). Data is reported for 'on-treatment' observation period. On-treatment observation period: from first administration and up until last trial contact, visit 7 or 14 days after last administration, whichever comes first. | From baseline (week 0) to visit 7 (week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Age | Change from baseline (week -2) in bone age at week 52 is presented. X-ray images of left hand and wrist for bone age assessment according to the Greulich and Pyle atlas were taken. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | Baseline (week -2), week 52 | 
| Change in Height Standard Deviation Score (HSDS) | Change from baseline (week 0) in HSDS at week 52 is presented. HSDS was derived using Centre for Disease Control and Prevention (CDC) standards. 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. Positive value in change from baseline in HSDS indicated that HSDS was better than baseline HSDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | Baseline (week 0), week 52 | 
| Change in Height Velocity Standard Deviation Score (HV SDS) | Change from baseline (week 0) in HV SDS at week 52 is presented. HV SDS was calculated using the formula: HV SDS = (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 HV SDS 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. Positive value in change from baseline in HV SDS indicated that HV SDS was better than baseline HV SDS. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | Baseline (week 0), week 52 | 
| Change in Fasting Plasma Glucose (FPG) at Week 52 | Change from baseline (week -2) in FPG at week 52 is presented. | Baseline (week -2), week 52 | 
| Change in FPG at Week 104 |  | Baseline (week -2), week 104 | 
| Change in FPG at Week 156 |  | Baseline (week -2), week 156 | 
| Change in FPG at Week 208 |  | Baseline (week -2), week 208 | 
| Change in Homeostatic Model Assessment Steady State Beta Cell Function (HOMA-B) at Week 52 | Change from baseline (week -2) in HOMA-B at week 52 is presented. HOMA-B is a measure of the beta cell function and was calculated as follows: HOMA-B = (20 * fasting insulin (picomoles per liter [pmol/L]) * 1/6(microunit per milliliter [µU/mL]))/ FPG(mmol/L)-3.5). Negative change from baseline in HOMA-B indicated a worse outcome. | Baseline (week -2), week 52 | 
| Change in HOMA-B at Week 104 |  | Baseline (week -2), week 104 | 
| Change in HOMA-B at Week 156 |  | Baseline (week -2), week 156 | 
| Change in HOMA-B at Week 208 |  | Baseline (week -2), week 208 | 
| Change in Homeostatic Model Assessment Insulin Resistance (HOMA-IR) at Week 52 | Change from baseline (week -2) in HOMA-IR at week 52 is presented. HOMA-IR is an evaluation of the insulin resistance and was calculated as HOMA-IR = fasting insulin (pmol/L) * 1/6(µU/mL) * FPG(mmol/L) / 22.5. Positive change from baseline in HOMA-IR indicated a worse outcome. | Baseline (week -2), week 52 | 
| Change in HOMA-IR at Week 104 |  | Baseline (week -2), week 104 | 
| Change in HOMA-IR at Week 156 |  | Baseline (week -2), week 156 | 
| Change in HOMA-IR at Week 208 |  | Baseline (week -2), week 208 | 
| Change in Glycated Haemoglobin (HbA1c) at Week 52 | Change from baseline (week -2) in HbA1c at week 52 is presented. | Baseline (week -2), week 52 | 
| Change in HbA1c at Week 104 |  | Baseline (week -2), week 104 | 
| Change in HbA1c at Week 156 |  | Baseline (week -2), week 156 | 
| Change in HbA1c at Week 208 |  | Baseline (week -2), week 208 | 
| Change in Insulin-like Growth Factor I (IGF-I) Standard Deviation Score (SDS) at Week 52 | Change from baseline (week 0) in IGF-I SDS at week 52 is presented. 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. For participants with low IGF-I SDS at baseline, a positive change from baseline in IGF-I SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | Baseline (week 0), week 52 | 
| Change in IGF-I SDS at Week 104 |  | Baseline (week 0), week 104 | 
| Change in IGF-I SDS at Week 156 |  | Baseline (week 0), week 156 | 
| Change in IGF-I SDS at Week 208 |  | Baseline (week 0), week 208 | 
| Change in Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Standard Deviation Score (SDS) at Week 52 | Change from baseline (week 0) in IGFBP-3 SDS at week 52 is presented. 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. For participants with low IGFBP-3 SDS at baseline, a positive change from baseline in IGFBP-3 SDS indicated a better outcome. Data is reported for 'in-trial' observation period. In-trial observation period: from first administration and up until visit 7 or last trial contact, whichever comes first. | Baseline (week 0), week 52 | 
| Change in IGFBP-3 SDS at Week 104 |  | Baseline (week 0), week 104 | 
| Change in IGFBP-3 SDS at Week 156 |  | Baseline (week 0), week 156 | 
| Change in IGFBP-3 SDS at Week 208 |  | Baseline (week 0), week 208 |