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)

Phase 3

Terminated

Conditions: Infant, Small for Gestational Age

Interventions: Drug: Recombinant human growth hormone (r-hGH)

Registration Number: NCT01067352

Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief 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.

Detailed 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 & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 25

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A (A1)	Recombinant human growth hormone (r-hGH)	Participants were allocated to Group A if were still third percentile for height (according to the Tanner reference table) at the age of 4-6 years. Group A would be then randomized to receive Saizen at the daily dose of 0.035 milligram (mg)/kilogram (kg) (Group A1) or no treatment (Group A2) for two years.

Primary Outcome Measures

Name	Time	Method
Correlation Between Gene Expression Profiling and Catch-up Growth in Small for Gestational Age (SGA) Children	Baseline and Week 48	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation	Baseline through Week 96	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.
Percentage of Untreated Participants Who Showed a Spontaneous Catch-up Growth	Baseline through Week 96	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.