Investigating Efficacy and Safety of Once-weekly NNC0195-0092 (Somapacitan) Treatment Compared to Daily Growth Hormone Treatment (Norditropin® FlexPro®) in Growth Hormone Treatment naïve Pre-pubertal Children With Growth Hormone Deficiency

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 (somapacitan) treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency. The trial consists of a 26 week main trial period, followed by a 26 week extension trial period, a 104 week safety extension period, a 208 week longterm safety extension trial period and a 30 day follow up period. Participants receive NNC0195-0092 (somapacitan) (0.04 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. Two additional age groups, cohort II (age below 2 years and 26 weeks at screening) and cohort III (above 9 years (girls)/ above 10 years (boys) and equal to or below 17 years at screening) are included in the 208 week long-term safety extension trial period only.

Official Title
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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

Conditions
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Growth Hormone Disorder, Growth Hormone Deficiency in Children

Intervention / Treatment
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* Drug: somapacitan
* Drug: Norditropin® FlexPro® pen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cohort I: 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 Cohort II: Below 2 years and 26 weeks and a minimum weight of 5 kg at screening. Confirmed diagnosis of GHD, the GHD diagnosis must be confirmed by investigator according to local practice. For GH treatment naïve subjects, no prior exposure to GH therapy and/or IGF-I treatment. For GH treatment naïve subjects, IGF-1 SDS below -1.0 at screening, compared to age and sex normalized range according to central laboratory measurements. Cohort III: Age: Girls: Above 9.0 years and below or equal to 17.0 years at screening. Boys: Above 10.0 years and below or equal to 17.0 years at screening. Confirmed diagnosis of GHD for GH treatment naïve subjects, confirmed diagnosis within 12 months prior to screening as determined by two different GH stimulation tests, defined as a peak GH level of equal to or below 7.0 ng/ml. For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed. FOR JAPAN ONLY: Confirmed diagnosis of GHD within 12 months prior to screening as determined by one GH stimulation tests for patients with intracranial organic disease or symptomatic hypoglycaemia and two different GH stimulation test for other patients, defined as a peak GH level of equal to or below 6 ng/ml by assay using recombinant GH standard. for non-GH treatment naïve subjects, confirmed GHD diagnosis by investigator according to local practice For GH treatment naïve subjects, no prior exposure to GH therapy and/or IGF-I treatment. Open epiphyses; defined as bone age below 14 years for females and bone age below 16 years for males. Exclusion Criteria: Any clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing/length 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

Ages Eligible for Study
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Minimum Age: 30 Months
Maximum Age: 10 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinded NNC0195-0092 (somapacitan) (0.04 mg/kg/week)<br>Participants receive NNC0195-0092 (somapacitan) (0.04 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. | Drug: somapacitan<br>* Administered subcutaneously (s.c., under the skin) once-weekly.<br>* Other names: NNC0195-0092;|
| Experimental: Blinded NNC0195-0092 (somapacitan) (0.08 mg/kg/week)<br>Participants receive NNC0195-0092 (somapacitan) (0.08 mg/kg/week) during the main trial and the extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the safety extension and the long-term safety extension periods. | Drug: somapacitan<br>* Administered subcutaneously (s.c., under the skin) once-weekly.<br>* Other names: NNC0195-0092;|
| Experimental: Blinded NNC0195-0092 (somapacitan) (0.16 mg/kg/week)<br>Participants receive the same dose (0.16 mg/kg/week) of NNC0195-0092 (somapacitan) during all 4 trial periods. | Drug: somapacitan<br>* Administered subcutaneously (s.c., under the skin) once-weekly.<br>* Other names: NNC0195-0092;|
| Active Comparator: Open labelled daily Norditropin® (0.034 mg/kg/day)<br>Participants receive Norditropin during the main trial, the extension period and the safety extension period and thereafter NNC0195-0092 (somapacitan) (0.16 mg/kg/week) during the long-term safety extension periods. | Drug: somapacitan<br>* Administered subcutaneously (s.c., under the skin) once-weekly.<br>* Other names: NNC0195-0092;Drug: Norditropin® FlexPro® pen<br>* Administered subcutaneously (s.c., under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort I: Height velocity (HV) during the first 26 weeks of treatment, measured as standing height with stadiometer | cm/year | Week 0-26 | 
| Cohort II and III: Incidence of adverse events, including injection site reactions, in children with GHD | Number of events | During 208 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in height standard deviation score (SDS) | Typically -10 to +10 | Week 0-26 | 
| Change in height standard deviation score (SDS) | Typically -10 to +10 | Week 0-52 | 
| Change in height standard deviation score (SDS) | Typically -10 to +10 | Week 26-52 | 
| Change in HV (height velocity) SDS | Typically -10 to +10. Baseline (week 0) HV SDS is derived from reported pre-trial standing height measured at minimum 6 months and maximum 18 months prior to screening visit to standing height at baseline (week 0) | Week 0-26 | 
| Change in HV (height velocity) SDS | Baseline (week 0) HV SDS is derived from reported pre-trial standing height measured at minimum 6 months and maximum 18 months prior to screening visit to standing height at baseline (week 0) | Week 0-52 | 
| Insulin-like growth factor 1 (IGF-I) SDS | Typically -10 to +10 | Week 0-26 | 
| Insulin-like growth factor 1 (IGF-I) SDS | Typically -10 to +10 | Week 0-52 | 
| Insulin-like growth factor 1 (IGF-I) SDS | Typically -10 to +10 | Week 26-52 | 
| Insulin-like growth factor binding protein 3 (IGFBP-3) SDS | Typically -10 to +10 | Week 0-26 | 
| Insulin-like growth factor binding protein 3 (IGFBP-3) SDS | Typically -10 to +10 | Week 0-52 | 
| Insulin-like growth factor binding protein 3 (IGFBP-3) SDS | Typically -10 to +10 | Week 26-52 | 
| Height velocity | cm/year, derived from standing height from baseline (week 0) to week 52 | Week 52 | 
| Bone age | X-Ray of left hand and wrist, central assessed according to Greulich & Pyle atlas progression vs. chronological age | Week 52 | 
| Serum NNC0195-0092 (somapacitan) concentrations | ng/mL | 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) | The scores range from 0-100. A lower score indicates a better health state. | Week 0-26 | 
| 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) | The scores range from 0-100. A lower score indicates a better health state. | Week 0-52 | 
| Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O) | The scores range from 0-100. A lower score indicates a better health state. | Week 26 | 
| Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Observer (TB-CGHD-O) | The scores range from 0-100. A lower score indicates a better health state. | Week 52 | 
| Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P) | The scores range from 0-100. A lower score indicates a better health state. | Week 26 | 
| Total score of The Treatment Burden Measure - Child Growth Hormone Deficiency - Parent/Guardian (TB-CGHD-P) | The scores range from 0-100. A lower score indicates a better health state. | Week 52 | 
| Incidence of adverse events, including injection site reactions | Number of events | Week 364 | 
| Occurrence of anti-NNC0195-0092 (somapacitan) antibodies | Yes/no | Week 364 | 
| Occurrence of anti-hGH antibodies | Yes/no | Week 364 |