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) (SAIZEN in SGA)

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)

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.

Study Overview

• Status: Terminated
• Conditions: Infant, Small for Gestational Age
• Intervention / Treatment: Drug: Recombinant human growth hormone (r-hGH)

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

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy
    • Merck Serono S.p.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (A1); 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.	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.; Other Names: Saizen
No Intervention: Group A (A2); 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 no treatment (Group A2) for two years.
No Intervention: Group B; Participants were allocated to Group B being third percentile (thus showing a spontaneous catch-up growth).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck Serono S.P.A., Italy

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: February 10, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Estimate): December 27, 2013
• Last Update Submitted That Met QC Criteria: December 2, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Growth hormone; Saizen; Infant, small for gestational age
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: IMP23681