Safety and Efficacy of Omnitrope® (rhGH) in Short Children Born Small for Gestational Age (SGA)

Long-term Phase IV Multicentre Study on the Safety and Efficacy of Omnitrope® (rhGH) in Short Children Born Small for Gestational Age (SGA)

This study is performed to investigate the long-term safety, in particular the diabetogenic potential and immunogenicity of rhGH therapy in short children born small for gestational age (SGA).

Study Overview

• Status: Completed
• Conditions: Small for Gestational Age
• Intervention / Treatment: Drug: Omnitrope

Detailed Description

Prospective, open label, non-comparative, multicenter study. Short children born SGA were to be treated until they reached final height, but treatment could be discontinued earlier if medically indicated or if there was inadequate response to treatment.

• Study Type: Interventional
• Enrollment (Actual): 278
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Sandoz Investigational Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Sandoz Investigational Site
  • Usti nad Labem, Czechia, 400 11
    • Sandoz Investigational Site
  • Praha
    • Praha 5, Praha, Czechia, 150 06
      • Sandoz Investigational Site
• Georgia
  • Tbilisi, Georgia, 144
    • Sandoz Investigational Site
• Germany
  • Bayern
    • Muenchen, Bayern, Germany, 80337
      • Sandoz Investigational Site
  • Nordrhein Westfalen
    • Sankt Augustin, Nordrhein Westfalen, Germany, 53757
      • Sandoz Investigational Site
• Hungary
  • Budapest, Hungary, 1023
    • Sandoz Investigational Site
  • Budapest, Hungary, 1094
    • Sandoz Investigational Site
  • Gyor, Hungary, 9024
    • Sandoz Investigational Site
  • Miskolc, Hungary, 3526
    • Sandoz Investigational Site
  • Csongrad
    • Szeged, Csongrad, Hungary, 6720
      • Sandoz Investigational Site
• Poland
  • Gdansk, Poland, 80-952
    • Sandoz Investigational Site
  • Katowice, Poland, 40-752
    • Sandoz Investigational Site
  • Krakow, Poland, 30-663
    • Sandoz Investigational Site
  • Lodz, Poland, 93-338
    • Sandoz Investigational Site
  • Szczecin, Poland, 71-252
    • Sandoz Investigational Site
  • Warszawa, Poland, 04-730
    • Sandoz Investigational Site
  • Wroclaw, Poland, 51-312
    • Sandoz Investigational Site
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 50-368
      • Sandoz Investigational Site
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-667
      • Sandoz Investigational Site
  • Podkarpackie
    • Rzeszow, Podkarpackie, Poland, 35-301
      • Sandoz Investigational Site
  • Slaskie
    • Katowice, Slaskie, Poland, 40-752
      • Sandoz Investigational Site
    • Zabrze, Slaskie, Poland, 41-800
      • Sandoz Investigational Site
  • Swietokrzyskie
    • Kielce, Swietokrzyskie, Poland, 25734
      • Sandoz Investigational Site
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-572
      • Sandoz Investigational Site
• Romania
  • Bucuresti, Romania, 011461
    • Sandoz Investigational Site
  • Bucuresti, Romania, 020395
    • Sandoz Investigational Site
  • Craiova, Romania, 200642
    • Sandoz Investigational Site
  • Iaşi, Romania, 700111
    • Sandoz Investigational Site
  • Cluj
    • Cluj Napoca, Cluj, Romania, 400370
      • Sandoz Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pre-pubertal (Tanner stage I) children born SGA Boys: 4 years of age or older Girls: 4 years of age or older
• Growth disturbance defined as current height SDS < -2.5 (and parental adjusted SDS <-1) for chronological age and sex according to country specific references.
• Birth weight and/or length below -2 standard deviations (SD) for gestational age

Exclusion Criteria:

• Onset of puberty
• Closed epiphyses
• Diabetes mellitus type I or type II
• Fasting blood glucose greater than 100 mg/dl or greater than 5.6 mmol/l measured in venous blood sample
• Abnormal findings in Oral Glucose Tolerance Test (OGTT) defined by greater than 140 mg/dl or greater than 7.8 mmol/l after 120 minutes
• Known IGF-I level above +2SD for sex and age
• Acute critical illness
• Previous treatment with any hGH preparation
• Treatment with antidiabetic medication (e.g. metformin, insulin)
• Drug abuse, substance abuse, or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omnitrope; All enrolled patients received Omnitrope. The median daily dose varied between 0.0340 and 0.0351 mg/kg/day and the maximum range was 0.000 to 0.040 mg/kg/day over all visits.	Drug: Omnitrope; All enrolled patients received Omnitrope. The median daily dose varied between 0.0340 and 0.0351 mg/kg/day and the maximum range was 0.000 to 0.040 mg/kg/day over all visits.; Other Names: Somatropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Development of Diabetes in Short Children Born SGA During Treatment	The development of diabetes in short children born SGA during treatment was evaluated based on the carbohydrate metabolism parameters FPG, HbA1c and OGTT (basal and 2-h plasma glucose). Only cases which were confirmed by the investigator were included.	throughout the study, approximately 13 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Height (H) (cm) From Baseline	Mean change in Height from baseline for all patients was reported.	Baseline, 3 months, 1 year, 2 years, 5 years and 9 years
Mean Change in Height Standard Deviation Score Over Time From Baseline	SDS reflects the deviation of a measured value from the mean value of normally growing children of the same sex and chronological age, expressed in units of the standard deviation (SD) of normally growing children of the same sex and chronological age. SDS was calculated according to the formula SDS=(X1-X2)/SD, where X1 is the measured value, X2 the mean value for the relevant chronological age and sex, and SD the reference standard deviation for the relevant sex and age. Refer to SAP page 14 for the formula and to Appendix B (H SDS) and D (HV SDS) for the applied reference Table. In general, a negative SDS indicates that the value is below average or mean and a positive value means it is above the average or mean. The calculated mean change compared to baseline reflects the catch-up growth over time towards average normal growth starting from below average.	Baseline, 3 months, 0.5 year, 9 months, 1 year, 1.25 years, 1.5 years, 1.75 years, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 12.5 years
Mean Change in Height Velocity (HV) (cm/Year) Over Time From Baseline	Mean change in Height velocity (HV) (cm/year) over time from baseline was reported.	Baseline, 3 months, 1 year, 2 years, 5 years and 9 years
Mean Change in Height Velocity Standard Deviation Score (HV SDS) Over Time From Baseline	SDS reflects the deviation of a measured value from the mean value of normally growing children of the same sex and chronological age, expressed in units of the standard deviation (SD) of normally growing children of the same sex and chronological age. SDS was calculated according to the formula SDS=(X1-X2)/SD, where X1 is the measured value, X2 the mean value for the relevant chronological age and sex, and SD the reference standard deviation for the relevant sex and age. Refer to SAP page 14 for the formula and to Appendix B (H SDS) and D (HV SDS) for the applied reference Table. In general, a negative SDS indicates that the value is below average or mean and a positive value means it is above the average or mean. The calculated mean change compared to baseline reflects the initial high increase in height velocity which remains positive over years, but is decreasing over time.	Baseline, 3 months, 0.5 year, 9 months, 1 year, 1.25 years, 1.5 years, 1.75 years, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 12.5 years
Mean Change in Serum IGF-1 Level (Nmol/L) From Baseline	Mean change in serum IGF-1 level (nmol/L) from baseline was reported.	Baseline, 3 months, 1 year, 2 years, 5 years and 9 years
Mean Change in IGFBP-3 Levels (Nmol/L) From Baseline	Mean change in IGFBP-3 levels (nmol/L) from baseline was reported.	Baseline, 3 months, 1 year, 2 years, 5 years and 9 years
Number of Participants With the Development of Anti-rhGH Antibodies During Omnitrope Treatment	Number of participants with the development of anti-rhGH antibodies with positive test result were reported.	throughout the study, approximately 13 years

Collaborators and Investigators

• Sponsor: Sandoz
• Investigators: Study Chair: Sandoz Biopharmaceuticals, Sandoz GmbH

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2008
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): March 25, 2022

Study Registration Dates

• First Submitted: October 1, 2007
• First Submitted That Met QC Criteria: October 1, 2007
• First Posted (Estimated): October 2, 2007

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Small for Gestational Age, Omnitrope®/Somatropin, rhGH,SGA
• Other Study ID Numbers: CEP00-401; 2006-002506-58 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com