Predictive Markers in Chinese Growth Hormone Deficiency (GHD) Children Treated With Saizen® - Full Text View

Purpose

This is an open-label, prospective, multicentric, non-comparative, non-randomized Phase IV interventional study in which subjects pre-diagnosed with Growth Hormone Deficiency (GHD) were treated for 4 weeks with Saizen to compare the response between GHD children born appropriate for gestational age (AGA) and those born small for gestation age (SGA) after 4 weeks of Saizen therapy.

Condition	Intervention	Phase
Dwarfism, Pituitary	Drug: Recombinant human growth hormone (r-hGH)	Phase 4

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient Pre-pubertal Children Treated With Saizen®

Resource links provided by NLM:

Genetics Home Reference related topics: combined pituitary hormone deficiency isolated growth hormone deficiency metatropic dysplasia pseudoachondroplasia

MedlinePlus related topics: Diabetes Medicines Dwarfism

Drug Information available for: Somatropin

U.S. FDA Resources

Further study details as provided by Merck KGaA:

Primary Outcome Measures:

Change From Baseline in Serum Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) Levels at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) was calculated as logarithm (log) 10 actual value of IGF-1 - log 10 (mean reference value of IGF-1) divided by log10 reference standard deviation of IGF-1.

Secondary Outcome Measures:

Change From Baseline in Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) Levels at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Change From Baseline in Fasting Glucose at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Change From Baseline in Fasting Insulin at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Test at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
HOMA-IR is used to assess insulin resistance and calculated by an empirical mathematical formula based on fasting plasma glucose and fasting plasma insulin levels. HOMA-IR = fasting plasma insulin (picomole/liter [pmol/L]) * fasting plasma glucose (millimole/liter [mmol/L]) divided by 22.5.
Change From Baseline in Lipid Profile at Week 4 [ Time Frame: Baseline and Week 4 ] [ Designated as safety issue: No ]
Total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides levels were evaluated.

Enrollment:	214
Study Start Date:	March 2007
Estimated Study Completion Date:	April 2009
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Recombinant human growth hormone (r-hGH) administered at dose of 0.033 milligram/kilogram (mg/kg) body weight (0.1 International Unit [IU]/kg body weight) per day by subcutaneous injection.

Other Name: Saizen

Detailed Description:

The response to growth hormone (GH) treatment, short-term as well as long-term, displays considerable inter individual variability. This is particularly evident for the endpoint of paediatric GH administration, that is (i.e.) the growth response, which is pronounced in children who are affected by GHD. This is an open-label, multicentric study in which subjects pre-diagnosed with GHD were treated for 4 weeks with Saizen. Two hundred fourteen GHD evaluable pre-pubertal subjects were planned to be recruited in approximately 9 sites in China. Demographic data, medical history, tanner stage, physical examination, body weight, height, bone age measurement, body mass index, review of baseline medications and procedures and blood sampling were performed at baseline visit, end of treatment visit (week 4) and at 4 week follow-up visit.

OBJECTIVES

Primary objective:

To compare the response between GHD children born AGA and those born SGA after 4 weeks of Saizen therapy

Secondary Objectives:

To explore the contribution of selected genes to the phenotype of GHD children
To explore the impact of gene polymorphisms on the levels of specific serum biomarkers in GHD children after 4 weeks of Saizen therapy
To explore the relationships between changes in gene expression and changes in serum biomarkers after 4 weeks of Saizen therapy and the spectrum of gene polymorphisms in GHD children

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female subjects with documented pre-established diagnosis of GHD with a GH peak response of <10 microgram/liter (mcg/L) with 2 GH stimulation tests, without priming with estradiol
Subjects with SGA defined as birth weight and/or length at least 2 standard deviations (SDs) below the mean for gestational age
Subjects with prepubertal status according to Tanner
Subjects with pre-established history of normal thyroid function or adequate substitution for at least 3 months
Subjects with weight for stature within the population specific normal range (>5th and <95th percentiles) for gender
Subjects with willingness and ability to comply with the protocol for the duration of the study
Subjects whose parents or guardians written informed consent given before any study-related procedure that was not part of the subjects normal medical care, with the understanding that the subject or parent/guardian might withdraw consent at any time without prejudice to future medical care. If the child was old enough to read and write, a separate assent form was given

Exclusion Criteria:

Subjects who acquired GHD due to central nervous system tumor, trauma, infection, infiltration (documented by imaging), and history of irradiation or cranial surgery
Subjects with previous treatment with GH, growth hormone releasing hormone (GHRH), anabolic steroids or any treatment affecting growth
Subjects who had previous treatment with corticosteroids, except in case of topical or inhaled corticosteroid administration for atopic disease. Corticosteroids for hormonal substitution were also allowed if the condition and the treatment regimen had been stable for at least 3 months
Subjects with severe associated pathology affecting growth such as malnutrition, malabsorption, or bone dysplasia
Subjects with chronic severe kidney disease
Subjects with chronic severe liver disease
Subjects with chronic infectious disease
Subjects with acute or severe illness during the previous 6 months
Subjects with significant concomitant illness that would interfere with participation or assessment in this study
Subjects who had active malignancy (except non-melanomatous skin malignancies that had undergone surgical excision and/or biopsy, diagnosis and treatment to resolution)
Subjects with history or active idiopathic intra-cranial hypertension (benign intracranial hypertension or pseudo-tumor cerebri)
Subjects with diabetes mellitus type I & II
Subjects with any autoimmune disease
Subjects who had previous screening failure in this study
Subjects who had used an investigational drug or participated in another clinical study within the last 3 months

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187550

Sponsors and Collaborators

Merck KGaA

Merck Serono Co., Ltd., China

Investigators

Study Director:

Medical Responsible

Merck Serono Co., Ltd., China

More Information

No publications provided

Responsible Party:	Merck KGaA
ClinicalTrials.gov Identifier:	NCT01187550 History of Changes
Other Study ID Numbers:	27709
Study First Received:	August 22, 2010
Results First Received:	May 9, 2012
Last Updated:	June 28, 2012
Health Authority:	China: Ethics Committee

Keywords provided by Merck KGaA:

Dwarfism, pituitary
Growth hormone

Additional relevant MeSH terms:

Dwarfism
Dwarfism, Pituitary
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases
Bone Diseases, Endocrine
Hypopituitarism

Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013