Genotropin Treatment In Very Young Children Born Small For Gestational Age

Study Overview
=================
Brief Summary
-----------------
To demonstrate the effect on height and psychomotor development of Growth Hormone treatment in very young children starting at an age of 2 years.

Official Title
-----------------
A Two Year Multicentre, Randomized Two Arm Study Of Genotropin Treatment In Very Young Children Born Small For Gestational Age: Early Growth And Neurodevelopment(Egn)

Conditions
-----------------
Infant, Small for Gestational Age

Intervention / Treatment
-----------------
* Drug: Genotropin (PN-180,307) Somatropin
* Drug: Control-no treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Caucasian male or female subjects aged between 19-29 months at Screening Visit 1. Born SGA (birth length and/or weight <-2 SD for gestational age, using country-specific standards). Height below -2.5 SD at screening (19-29 months of age). At least one measurement of length between 12 and 18 months of age. Normal karyotype in girls to exclude Turners syndrome. Exclusion Criteria: Severe Intra-Uterine Growth Retardation (IUGR) (birth length below - 4 SD for gestational age), if associated with dysmorphic features. Severe prematurity (Gestational Age (GA) <32 weeks of gestation). Ongoing catch-up growth (defined as growth velocity SDS at inclusion >0) based on at least 4 months measurement interval). Severe familial short stature defined as: Father's height below 155 cm or mother's height below 145 cm. Defined neurological defects and/or severe neurodevelopmental delay.

Ages Eligible for Study
-----------------
Minimum Age: 19 Months
Maximum Age: 29 Months

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: Active<br>The active treatment arm | Drug: Genotropin (PN-180,307) Somatropin<br>* Injectable Genotropin<br>|
| Experimental: Control<br>Control | Drug: Control-no treatment<br>* Control-no treatment<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Height Standard Deviation Score (SDS) at Month 24. | Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender. | Baseline and Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Growth Velocity SDS at Month 24. | The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender. | Baseline and Month 24 | 
| Change From Baseline in Height SDS at Month 12. | Height SDS was calculated at the relevant visit by means of the following formula: Height SDS = (participant height) - (normal height)/normal height standard deviation. Where participant height refers to the participant's height at the relevant visit, and normal height and the normal height standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for height SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. The scores were centred around zero. Negative score indicated a participant was smaller for their age/gender. | Baseline and Month 12 | 
| Change From Baseline in Growth Velocity SDS at Month 12. | The growth velocity SDS was calculated at the relevant visit by means of the following formula: Growth velocity SDS = (participant growth velocity) - (normal growth velocity)/normal growth velocity standard deviation. Where, participant growth velocity refers to the participant's growth velocity at the relevant visit, and normal growth velocity and the normal growth velocity standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. The change from Baseline value for growth velocity SDS was calculated as the difference between the parameter values at a specific visit, and the Baseline parameter values. A negative score indicated that a participant had slower growth for their age/gender. | Baseline and Month 12 | 
| Change From Baseline in Mental Development Using the Mental Development Index (MDI) of Bayley Scale at Month 12. | The Bayley Scale of Infant Development (BSID-II) measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the mental raw score which was used to calculate the MDI score. Possible MDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance. | Baseline and Month 12 | 
| Change From Baseline in Psychomotor Development Using the Psychomotor Development Index (PDI) of Bayley Scale at Month 12. | BSID-II measured the mental and psychomotor development and test behavior of participants from 1 to 42 months of age. The scale was used to describe the current developmental functioning of infants and to assist in diagnosis and treatment planning for infants with developmental delays or disabilities. The BSID-II provided the psychomotor raw score which was used to calculate the PDI score. Possible PDI scores ranged from 50-150. A score of 69 and below indicates significantly delayed performance, 70 to 84 indicates mildly delayed performance, 85 to 114 indicates normal limits and 115 and above indicates accelerated performance. | Baseline and Month 12 | 
| Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/ Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender. | Months 3, 6, 12, 18 and 24 | 
| Change From Baseline in Head Circumference SDS at Months 3, 6, 12, 18 and 24. | Head circumference SDS was calculated by means of the following formula = (Participant head circumference)-(Normal head circumference)/Normal head circumference standard deviation. Where participant head circumference refers to the participant's head circumference at the relevant visit, and normal head circumference and the normal head circumference standard deviation equals the population mean and standard deviation values for participants of a similar age and gender. A negative score indicated a participant had a smaller head circumference for their age/gender. | Baseline, Months 3, 6, 12, 18 and 24. | 
| Change From Baseline in Body Weight at Months 3, 6, 12, 18, and 24. | Body weight was measured at all the relevant visits. The change from Baseline in body weight was calculated as the difference between the parameter values at each visit, and the Baseline parameter values. | Baseline, Months 3, 6, 12, 18, and 24 | 
| Change From Baseline in Body Mass Index (BMI) at Months 3, 6, 12, 18, and 24. | Body mass index was calculated for all visits by means of the following formula: BMI (kg/m2) = Weight (kg)/(Height[m])2. The change from Baseline BMI was calculated as the difference between the parameter values at each visit, and the Baseline parameter values. | Baseline, Months 3, 6, 12, 18, and 24 |