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)

Condition(s) targeted: Infant, Small for Gestational Age

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

Phase: Phase 3

Status: Terminated

Sponsored by: Merck KGaA

Official(s) and/or principal investigator(s):
Medical Responsible, Study Director, Affiliation: Merck Serono S.P.A., Italy

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.

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)

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

Primary outcome: Correlation Between Gene Expression Profiling and Catch-up Growth in Small for Gestational Age (SGA) Children

Secondary outcome:

Percentage of Untreated Participants Who Showed a Spontaneous Catch-up Growth

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation

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

Minimum age: 4 Years. Maximum age: 6 Years. Gender(s): Both.

Criteria:

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

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

Starting date: February 2004
Last updated: December 2, 2013