Growth Hormone Treatment in Children Born Small for Gestational Age (SGA)

Study Overview
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Brief Summary
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This study is conducted in Japan. The aim of this trial is to assess the efficacy and safety of somatropin in children born small for gestational age (SGA) in Japan. In the main period, subjects will receive either active treatment for 104 weeks (two dosing regimens) or no treatment for 52 weeks followed by an extension period where subjects who received active treatment for 104 weeks (two years) will continue with the same treatment for further 156 weeks (three years) while those subjects who received no treatment for 52 weeks (one year) will be randomised to receive two dosing regimens for 208 weeks (four years). In total, subjects participate in trial for 260 weeks (five years). Main period is registered internally at Novo Nordisk as GHLIQUID-1516 while the extension period is registered as GHLIQUID-1517.

Official Title
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GHLIQUID-1516: A 104-week, Multi-centre, Randomised, Double-blind, Parallel-group, no Treatment Controlled (Open-label) Trial Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age / GHLIQUID-1517: A Long-term, Multi-centre, Randomised, Controlled, Double-blind, Parallel-group Trial, Investigating the Efficacy and Safety of Two Doses of NN-220 in Subjects With Short Stature Born Small for Gestational Age

Conditions
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Foetal Growth Problem, Small for Gestational Age

Intervention / Treatment
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* Drug: somatropin
* Drug: somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For MAIN period (GHLIQUID-1516): Born small for gestational age (SGA) with birth weight and birth length below the 10th percentile for gestational age, and additional either birth length below or equal to -2.0 standard deviation score (SDS) or birth weight below or equal to -2.0 SDS for gestational age Growth failure with height at -2.0 SDS or below for chronological age (CA) Normal growth hormone (GH) production, defined as peak GH level > 10 ng/mL in one GH provocation test For EXTENSION period (GHLIQUID-1517): Subjects who completed the main period Chronological age (CA) for boys at least 4 years, but maximum 11 years Chronological age (CA) for girls at least 4 years, but maximum 10 years Exclusion Criteria: Subjects with diabetes mellitus Subjects suffering from malignancy Several medical conditions

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 8 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.033 mg / NN-220<br>In the 156-week main period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime | Drug: somatropin<br>* 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge<br>|
| Experimental: 0.067 mg / NN-220<br>In the 156-week main period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime followed by a 104-week extension period where subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime | Drug: somatropin<br>* 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge<br>|
| No Intervention: No treatment<br>No somatropin (NN-220) treatment was given in the 52-week main period. Subjects was re-randomised to recive two dosing regimens (0.033 mg/kg/day or 0.067 mg/kg/day) in the 208-week extension period | |
| Experimental: No treatment --> 0.033 mg<br>In the 208-week extension period, subjects received 0.033 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period | Drug: somatropin<br>* 0.033 mg/kg/day of NN-220 for s.c. injection in cartridge<br>|
| Experimental: No treatment --> 0.067 mg<br>In the 208-week extension period, subjects received 0.067 mg/kg/day somatropin (NN-220) s.c. (under the skin) injected at bedtime after having received no somatromin (NN-220) treatment in the 52-week main period | Drug: somatropin<br>* 0.067 mg/kg/day of NN-220 for s.c. injection in cartridge<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 260 - Subjects Received NN220 Treatment for 5 Years | Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit | Week 0, week 260 | 
| Change in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Week 208 - Subjects Received NN220 Treatment for 4 Years | Height SDS for chronological age were derived as follow; {Height - mean (age, sex)}/ SD (age, sex), where mean (age, sex) and SD (age, sex) were mean and SD of height for corresponding chronological age and sex (data of those in 2000). Height SDS was calculated using mean of three height observations at corresponding visit | Week 0, week 208 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 5 Years | Yearly Height velocity SDS for chronological age were summarised and graphically presented | Weeks 0-260 | 
| Yearly Height Velocity SDS for Chronological Age - Subjects Received NN220 Treatment for 4 Years | Yearly Height velocity SDS for chronological age were summarised and graphically presented | Weeks 0-208 | 
| Change in Bone Age (Left Hand X-Ray) at Week 260 - Subjects Received NN220 Treatment for 5 Years | Bone age is measured as years and months (displayed as xx.x years). Change in Bone age = Bone age at 52*i weeks - Bone age at 52*(i-1) weeks, i=1, 2, …. | Week 0, week 260 | 
| Change in Bone Age (Left Hand X-Ray) at Week 208 - Subjects Received NN220 Treatment for 4 Years | Bone age is measured as years and months (displayed as xx.x years).Change in Bone age = Bone age at 52*i weeks - Bone age at 52*(i-1) weeks, i=1, 2, …. | Week 0, week 208 | 
| Adverse Events - Subjects Received NN220 Treatment for 5 Years | Occurrence of Adverse Events (AEs) during treatment period (TEAEs), occurrence of possibly/probably related AEs during the treatment period, and occurrence of Serious Adverse Events (SAEs) during the treatment period. An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product(s). An SAE is an experience that at any dose is fatal, life-threatening, disabling or which results in the patient being hospitalised or, if already in hospital, that hospitalisation is prolonged, or ocurrence of congenital anomaly | Weeks 0-260 | 
| Adverse Events - Subjects Received NN220 Treatment for 4 Years | Occurrence of Adverse Events (AEs) during treatment period (TEAEs), occurrence of possibly/probably related AEs during the treatment period, and occurrence of Serious Adverse Events (SAEs) during the treatment period. An AE is any undesirable medical event occurring to a subject in a clinical trial, whether or not related to the trial product(s). An SAE is an experience that at any dose is fatal, life-threatening, disabling or which results in the patient being hospitalised or, if already in hospital, that hospitalisation is prolonged, or ocurrence of congenital anomaly | Weeks 0-208 |