Genotropin Treatment In Very Young Children Born Small For Gestational Age (EGN)

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)

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

Study Overview

• Status: Completed
• Conditions: Infant, Small for Gestational Age
• Intervention / Treatment: Drug: Genotropin (PN-180,307) Somatropin; Drug: Control-no treatment

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • Universitair Ziekenhuis Brussel/Pediatrie
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen / Pediatrie
• Czech Republic
  • Olomouc, Czech Republic, 775 20
    • Fakultni Nemocnice Olomouc
  • Ostrava-Poruba, Czech Republic, 708 52
    • Fakultni nemocnice Ostrava, Detska klinika
  • Praha 5, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
• France
  • Toulouse Cedex 9, France, 31059
    • CHU Toulouse, Hôpital des Enfants, Service Endocrinologie
• Germany
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen, Kinder- und Jugendklinik
• Italy
  • Catania, Italy, 95125
    • Centro di Endocrinologia Pediatrica, Dipartimento di Pediatria
  • Messina, Italy, 98100
    • Policlinico Universitario, Istituto di Clinica Pediatrica
  • Milano, Italy, 20132
    • Dipartimento Materno Infantile, UO di Pediatria e Neonatologia
  • Roma, Italy, 00165
    • Dipartimento di Medicina Pediatrica, UO di Endocrinologia e Diabetologia
• Netherlands
  • Rotterdam, Netherlands, 3015 GJ
    • Sophia Children's Hospital
• Spain
  • Zaragoza, Spain, 50009
    • Hospital Miguel Servet
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Consorci Hospitalari Parc Taulí
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Hospital Virgen del Camino
• Sweden
  • Göteborg, Sweden
    • Drottning Silvias Barn Och Ungdomssjukhus
• Switzerland
  • CH-3010 Bern, Switzerland
    • Inselspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; The active treatment arm	Drug: Genotropin (PN-180,307) Somatropin; Injectable Genotropin
Experimental: Control	Drug: Control-no treatment; Control-no treatment

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• De Schepper J, Vanderfaeillie J, Mullis PE, Rooman R, Robertson A, Dilleen M, Gomez R, Wollmann HA. A 2-year multicentre, open-label, randomized, controlled study of growth hormone (Genotropin(R)) treatment in very young children born small for gestational age: Early Growth and Neurodevelopment (EGN) Study. Clin Endocrinol (Oxf). 2016 Mar;84(3):353-60. doi: 10.1111/cen.12968. Epub 2015 Nov 25.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 22, 2008
• First Submitted That Met QC Criteria: February 22, 2008
• First Posted (Estimate): March 3, 2008

Study Record Updates

• Last Update Posted (Estimate): November 4, 2014
• Last Update Submitted That Met QC Criteria: October 27, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: A6281287; 2007-003949-32 (EudraCT Number); SGA (Other Identifier: Alias Study Number)