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

Phase 3

Completed

• Conditions: Small Gestational Age (SGA)
• Interventions: Drug: Saizen®

• Registration Number: NCT00249821
• Lead Sponsor: Merck KGaA, Darmstadt, Germany

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-02-28
• Study First Submitted: 2005-11-04
• Study First Submitted QC: 2005-11-04
• Study First Posted: 2005-11-07
• Primary Completion: 2007-09-30
• Study Completion: 2007-09-30
• Results First Submitted: 2012-06-28
• Results First Submitted QC: 2012-10-09
• Results First Posted: 2012-10-10
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-28
• Last Update Posted: 2017-09-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saizen® 0.057 mg/kg/day	Saizen®	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)
Saizen® 0.035 mg/kg/day	Saizen®	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)

Primary Outcome Measures

Name	Time	Method
Height Velocity	Month 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Height-Standard Deviation Score (H-SDS) at Month 6 and Month 12	Baseline (randomization), 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.
Height Velocity-Standard Deviation Score (HV-SDS)	Month 6 and Month 12	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.
Insulin Like Growth Factor-1 (IGF-1) Levels	Baseline (randomization), Month 6 and Month 12
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Baseline (randomization) until Month 12	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).
Change From Baseline in Bone Age at Month 12	Baseline (randomization) and Month 12	Bone age was assessed by a left wrist X-Ray and evaluated by the investigator according to the Greulich and Pyle method.
Change From Baseline in Height at Month 6	Baseline (randomization) and Month 6
Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels	Baseline (randomization), Month 6 and Month 12