A Trial to Evaluate the Correlation Between Spontaneous Catch-up Growth, Clinical Response to Saizen (Recombinant Human Growth Hormone, r-hGH) and Gene Expression Profiling in Children Small for Gestational Age (SGA)

Infant, Small for Gestational Age Clinical Trial

— SAIZEN in SGA  

Official title:

An Open, Multicenter, Randomized, Controlled Trial to Evaluate the Correlation Between Spontaneous Catch-up Growth, Clinical Response to Saizen (Recombinant Human Growth Hormone, r-hGH) and Gene Expression Profiling in Children Small for Gestational Age (SGA)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01067352
• Other study ID #: IMP23681
• Status: Terminated
• Phase: Phase 3
• First received: February 10, 2010
• Last updated: December 2, 2013
• Start date: February 2004
• Est. completion date: July 2009

Study information

• Verified date: December 2013
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This open, multicentric, randomized, controlled study is planned to evaluate the correlation between gene expression, spontaneous catch-up growth and therapeutic response to Saizen in SGA children.

Description:

This open, multicentric, randomized, controlled study was planned to identify genes activated by hGH in SGA children responders to treatment (making it possible in the near future to better identify SGA children likely to benefit from hGH treatment). Furthermore, the study would hopefully allow to verify which genes were responsible of spontaneous catch-up growth in children with diagnosis of SGA at birth but above the third percentile for height at the age of 24 months, and if these genes were the same activated by hGH during the treatment in participants responders. Sixty children born at term (i.e. after the 37th completed week of gestation) and with a diagnosis of SGA (defined as a length less than tenth percentile according to the Italian reference table published by Bertini and Fabris) were planned to be enrolled in the study. Forty participants (group A) were still less than third percentile for height (according to the Tanner reference table) at the age of 24 months, the remaining 20 (group B) being more than or equal to third percentile (thus showing a spontaneous catch-up growth). Group A was randomized to receive Saizen at the daily dose of 0.067 mg/kg (Group A1) or no treatment (Group A2) for two years. All participants were to undergo full clinical examination and blood chemistry at baseline visit and visit after 1,6,12,18 and 24 months for a period of two years. Gene expression analysis using the Clontech Atlas Human Array was performed in all participants at baseline and after one year in order to identify the possible correlation between catch-up growth (either spontaneous or drug-induced) and expression of some genes.

OBJECTIVES

Primary objective:

• To evaluate the correlation between gene expression profiling and catch-up growth (either spontaneous or drug induced after one year of treatment) in SGA children.

Secondary Objectives:

• To evaluate the percentage of participants not treated who show a spontaneous catch-up growth during the two years of observation.

• To assess the safety and tolerability of early treatment with Saizen

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years to 6 Years

Eligibility

Inclusion Criteria:

• SGA at birth (defined as a length at birth equal or below the tenth percentile according to the Italian reference table of Bertini and Fabris)

• Age of 24 Months

• Caucasic

• Born at term (i.e. after the 37th completed week of gestation)

• Height equal or below (Group A) or up (Group B) the third percentile at the age of 24 months according to the Tanner reference table

• Sufficient GH secretion (more than 10 nanogram (ng)/milliliter (ml)) at least to one of the tests commonly used at that age (glucagon, Levo-dopa, arginine, clonidine, Growth Hormone Releasing Hormone (GHRH), GH integrated secretion)

• Normal level of Thyroid-stimulating hormone (THS), Free Triiodothyronine (FT3), Free Thyroxine (FT4), Insulin-like growth factor 1(IGF-1), insulin and haemoglobin A1c (HbA1c)

• Normal level of Immunoglobulin A (IgA)

• Children parents willing to comply with the protocol for the whole duration of the study

• A written Informed Consent before the baseline visit must be obtained from the parent(s) / legal guardian(s)

Exclusion Criteria:

• Congenital malformations (including Silver-Russel syndrome)

• Known abnormal karyotype, especially in girls

• Twins

• Severe psychomotor retardation

• Previous or ongoing treatment with anabolic steroids or r-hGH

• Treatments interfering with the immune system (including bacterial lysate)

• Severe chronic illnesses

• Autoimmune diseases

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infant, Small for Gestational Age

Intervention

Drug:
• Recombinant human growth hormone (r-hGH)
Recombinant human GH were administered subcutaneously (s.c) at the daily dose of 0.067 mg/kg of body weight to Group A1.

Locations

Country	Name	City	State
Italy	Merck Serono S.p.A.	Roma

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck Serono S.P.A., Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation Between Gene Expression Profiling and Catch-up Growth in Small for Gestational Age (SGA) Children	Gene expression profiling:analysis of ribonucleic acid (RNA) extracted from body tissue or fluids using Clontech Atlas Human Array to study level of activation of genes in tissue analyzed. Analysis was performed to identify possible correlation between catch-up growth (either spontaneous or drug-induced after Week 48) and therapeutic response to rhGH. Spontaneous catch up growth:shown by SGA participants having length more than third percentile at Week 96 without any treatment;drug induced growth was by SGA participants having length more than third percentile at Week 96 with drug treatment.	Baseline and Week 48	No
Secondary	Percentage of Untreated Participants Who Showed a Spontaneous Catch-up Growth	Spontaneous catch up growth was the growth shown by SGA participants having length more than third percentile at Week 96 without any study drug treatment.	Baseline through Week 96	No
Secondary	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation	AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug , SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued from the study due to AE were also recorded.	Baseline through Week 96	Yes