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

Small for Gestational Age Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00537914
• Other study ID #: CEP00-401
• Secondary ID: 2006-002506-58
• Status: Completed
• Phase: Phase 4
• Start date: February 6, 2008
• Est. completion date: March 25, 2022

Study information

• Verified date: August 2023
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 278
• Est. completion date: March 25, 2022
• Est. primary completion date: March 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Small for Gestational Age

Intervention

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.

Locations

Country	Name	City	State
Belgium	Sandoz Investigational Site	Edegem	Antwerpen
Czechia	Sandoz Investigational Site	Hradec Kralove
Czechia	Sandoz Investigational Site	Praha 5	Praha
Czechia	Sandoz Investigational Site	Usti nad Labem
Georgia	Sandoz Investigational Site	Tbilisi
Germany	Sandoz Investigational Site	Muenchen	Bayern
Germany	Sandoz Investigational Site	Sankt Augustin	Nordrhein Westfalen
Hungary	Sandoz Investigational Site	Budapest
Hungary	Sandoz Investigational Site	Budapest
Hungary	Sandoz Investigational Site	Gyor
Hungary	Sandoz Investigational Site	Miskolc
Hungary	Sandoz Investigational Site	Szeged	Csongrad
Poland	Sandoz Investigational Site	Bydgoszcz	Kujawsko-pomorskie
Poland	Sandoz Investigational Site	Gdansk
Poland	Sandoz Investigational Site	Katowice
Poland	Sandoz Investigational Site	Katowice	Slaskie
Poland	Sandoz Investigational Site	Kielce	Swietokrzyskie
Poland	Sandoz Investigational Site	Krakow
Poland	Sandoz Investigational Site	Lodz
Poland	Sandoz Investigational Site	Poznan	Wielkopolskie
Poland	Sandoz Investigational Site	Rzeszow	Podkarpackie
Poland	Sandoz Investigational Site	Szczecin
Poland	Sandoz Investigational Site	Warszawa
Poland	Sandoz Investigational Site	Wroclaw
Poland	Sandoz Investigational Site	Wroclaw	Dolnoslaskie
Poland	Sandoz Investigational Site	Zabrze	Slaskie
Romania	Sandoz Investigational Site	Bucuresti
Romania	Sandoz Investigational Site	Bucuresti
Romania	Sandoz Investigational Site	Cluj Napoca	Cluj
Romania	Sandoz Investigational Site	Craiova
Romania	Sandoz Investigational Site	Iasi

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Countries where clinical trial is conducted

Belgium,  Czechia,  Georgia,  Germany,  Hungary,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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