Optimization of the Dosage Regimen of Growth Hormone Therapy in Children Born Small for Gestational Age

Study Overview
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Brief Summary
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Multicentric, open-label, randomized, pilot comparative study in parallel groups comparing 1 group of subjects receiving 0.057 milligram/kilogram/day (mg/kg/day) or 0.40 mg/kg/week of Saizen® during 1 year to 1 group receiving 0.035 mg/kg/day (0.24 mg/kg/week) of Saizen® during 1 year after an initial 3-year treatment of recombinant human growth hormone (r-hGH) therapy with 0.057 mg/kg/day in both groups.

Official Title
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Optimization of the Dosage Regimen With Growth Hormone Therapy in Children Born Small for Gestational Age. An Open Label, Randomized, Pilot Study, Comparing in Children Treated for 3 Years, the Efficacy of a Saizen® Treatment at the Same Dose Versus a Lower Maintenance Dose Prolonged During 1 Additional Year.

Conditions
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Small Gestational Age (SGA)

Intervention / Treatment
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* Drug: Saizen®
* Drug: Saizen®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible for inclusion / randomization into this study, the subjects must fulfill all of the following criteria (if there is no inclusion phase, the inclusion criteria will be considered as inclusion criteria for randomization): Written consent form signed by the parents / legal guardian, and child if possible Subject born SGA and receiving a r-hGH therapy for this pathology Recombinant human growth hormone (r-hGH) started at the maximal chronological age of 7 years for girls and 8 years for boys Treatment with r-hGH started for at least 30 months and less than 36 months at 0.057 mg/kg/day Height gain during the first 2 years of GH treatment > 1 SD compared with the initial value Exclusion Criteria: To be eligible for inclusion in this study the subjects must not meet any of the following criteria: Known hypersensitivity to Somatropin or any of the excipients Active neoplasia (either newly diagnosed or recurrent) Intracranial hypertension Known diabetes mellitus Proliferative or preproliferative diabetic retinopathy Evidence of any progression or recurrence of an underlying intra-cranial space occupying lesion Obesity defined as degree 1 on the corpulence curves Precocious puberty Pubertal status: Tanner breast development stage > 2 for girls, and testicular volume > 4 milliliter (mL) or testicular length > 3 centimeter (cm) and/or testosterone value >1 nanomole/liter [nmol/L] (0.29 gram/mL [g/mL]) for boys For girls > 9 years and Tanner breast development stage 1: uterine size > 35 millimeter (mm) Severe chronic concomitant illness such as chronic renal failure, cystic fibrosis Concomitant corticoid treatment or levothyroxine treatment other than substitutive treatment, topical or inhaled treatment Participation to any clinical study within the 30 days preceding study entry

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saizen® 0.057 mg/kg/day<br>Subjects who met all inclusion/exclusion criteria were randomly assigned to 0.057 mg/kg/day in this multi-center study. Subjects were stratified at randomization according to the Height-Standard Deviation Score (H-SDS) at this time (less than [<] -2 SDS or greater than [>] -2 SDS) | Drug: Saizen®<br>* Saizen® [somatropin (recombinant deoxyribonucleic acid [rDNA] origin) for injection], a r-hGH, is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone.<br>* Other names: somatropin;|
| Experimental: Saizen® 0.035 mg/kg/day<br>Subjects who met all inclusion/exclusion criteria were randomly assigned to 0.035 mg/kg/day in this multi-center study. Subjects were stratified at randomization according to the H-SDS at this time (< -2 SDS or > -2 SDS) | Drug: Saizen®<br>* Saizen® [somatropin (rDNA origin) for injection], a r-hGH, is indicated for the treatment of children with growth failure due to inadequate secretion of endogenous growth hormone.<br>* Other names: somatropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height Velocity | Height Velocity (HV) is the change in height since the previous year´s measurement and more precisely: HV = {(h-hp)/(d-dp)} * 365.25 [centimeter (cm)/year] where h is current height in cm, hp is previous height in cm, closest to 1 year previous, d is the current date and dp is the date of measurement of previous height, closest to 1 year previous. Additionally, d and dp have to be within 0.6 years and 1.5 years. HV is the mean height velocity over the interval between d and dp but is displayed as HV at d. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12 | Height-Standard Deviation Score (H-SDS) was calculated as height minus mean (age-and sex-matched reference) divided by standard deviation (SD) [age and sex-matched reference]. Greater H-SDS indicates greater height. | Baseline (randomization), Month 6 and Month 12 | 
| Height Velocity-Standard Deviation Score (HV-SDS) | Height Velocity-Standard Deviation Score (HV-SDS) was calculated as height velocity minus reference mean height velocity divided by SD of the reference mean height velocity. Greater HV-SDS indicates greater height velocity. | Month 6 and Month 12 | 
| Change From Baseline in Height at Month 6 |  | Baseline (randomization) and Month 6 | 
| Change From Baseline in Bone Age at Month 12 | Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method. | Baseline (randomization) and Month 12 | 
| Insulin Like Growth Factor-1 (IGF-1) Levels |  | Baseline (randomization), Month 6 and Month 12 | 
| Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels |  | Baseline (randomization), Month 6 and Month 12 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Adverse Events (AEs): Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. TEAEs: AEs that occur during treatment with the Investigational Medicinal Product (IMP). | Baseline (randomization) until Month 12 |