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Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®

Primary Purpose

Growth Hormone Deficiency, Turner Syndrome

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Saizen
Saizen
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Growth Hormone Deficiency

Eligibility Criteria

2 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: One of the following diagnoses and candidacy for SAIZEN® therapy: A) GHD: documented pre-established diagnosis of GHD with a growth hormone (GH) peak response of <10 microgram per liter (mcg/L) with 2 GH stimulation tests, without priming with oestradiol. B) Turner syndrome: documented pre-established diagnosis by karyotype. Prepubertal status according to Tanner Pre-established history of normal thyroid function or adequate substitution for at least 3 months. Weight for stature within the population specific normal range (>5th and <95th percentiles) for gender Willingness and ability to comply with the protocol for the duration of the study. Parent's or guardian's written informed consent, given before any study related procedure that is not part of the subject's normal medical care, with the understanding that the subject or parent/guardian may withdraw consent at any time without prejudice to future medical care. If the child is old enough to read and write, a separate assent form will be given. Exclusion Criteria: Acquired GHD due to central nervous system tumour, trauma, infection, infiltration (documented by imaging), and history of irradiation or cranial surgery Previous treatment with GH, growth hormone-releasing hormone (GHRH), anabolic steroids or any treatment affecting growth. Previous treatment with corticosteroids, except in case of topical or inhaled corticosteroid administration for atopic disease. Corticosteroids for hormonal substitution are also allowed if the condition and the treatment regimen have been stable for at least 3 months. Severe associated pathology affecting growth such as malnutrition, malabsorption, or bone dysplasia. Chronic severe kidney disease. Chronic severe liver disease. Chronic infectious disease. Acute or severe illness during the previous 6 months. Significant concomitant illness that would interfere with participation or assessment in this study. Active malignancy (except non-melanomatous skin malignancies that have undergone surgical excision and/or biopsy, diagnosis and treatment to resolution) History or active Idiopathic intra-cranial hypertension (benign intracranial hypertension or pseudo-tumor cerebri). Diabetes Mellitus type I & II. Any autoimmune disease. Previous screening failure in this study. Use of an investigational drug or participation in another clinical study within the last three months.

Sites / Locations

  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical InformationOffice
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office
  • Local Medical Information Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Turner Syndrome (TS)

Growth Hormone Deficiency (GHD)

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1
IGF-1 SDS was calculated using the Elmlinger reference method. Change in within subject IGF-1 levels (standard deviation scores) at Month 1 from Baseline was assessed. Descriptive statistics were determined for the Baseline and Month 1 assessments, and also for the level of change between these two assessments. If either the Baseline or Month 1 IGF-1 level was missing, then the within-subject change in IGF-1 was assumed to be missing.

Secondary Outcome Measures

Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
Change From Baseline in Fasting Glucose Levels at Month 1
Change From Baseline in Fasting Insulin Levels at Month 1
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1
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 Bone Alkaline Phosphatase Levels at Month 1

Full Information

First Posted
November 18, 2005
Last Updated
March 23, 2018
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT00256126
Brief Title
Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®
Official Title
A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children Treated With SAIZEN®
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
May 31, 2005 (Actual)
Primary Completion Date
September 30, 2007 (Actual)
Study Completion Date
September 30, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

5. Study Description

Brief Summary
The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Hormone Deficiency, Turner Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
318 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Turner Syndrome (TS)
Arm Type
Experimental
Arm Title
Growth Hormone Deficiency (GHD)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Saizen
Intervention Description
Subjects with TS will receive SAIZEN® as subcutaneous injection at a dose of 0.050 milligram per kilogram (mg/kg) of body weight per day (within the recommended dosage 0.045-0.050 mg/kg body weight) for a period of 1 month
Intervention Type
Drug
Intervention Name(s)
Saizen
Intervention Description
Subjects with GHD will receive SAIZEN® as subcutaneous injection at a dose of 0.035 mg/kg of body weight per day (within the recommended dosage 0.025-0.035 mg/kg body weight) for a period of 1 month.
Primary Outcome Measure Information:
Title
Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1
Description
IGF-1 SDS was calculated using the Elmlinger reference method. Change in within subject IGF-1 levels (standard deviation scores) at Month 1 from Baseline was assessed. Descriptive statistics were determined for the Baseline and Month 1 assessments, and also for the level of change between these two assessments. If either the Baseline or Month 1 IGF-1 level was missing, then the within-subject change in IGF-1 was assumed to be missing.
Time Frame
Baseline, Month 1
Secondary Outcome Measure Information:
Title
Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
Time Frame
Baseline, Month 1
Title
Change From Baseline in Fasting Glucose Levels at Month 1
Time Frame
Baseline, Month 1
Title
Change From Baseline in Fasting Insulin Levels at Month 1
Time Frame
Baseline, Month 1
Title
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1
Description
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.
Time Frame
Baseline, Month 1
Title
Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1
Time Frame
Baseline, Month 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: One of the following diagnoses and candidacy for SAIZEN® therapy: A) GHD: documented pre-established diagnosis of GHD with a growth hormone (GH) peak response of <10 microgram per liter (mcg/L) with 2 GH stimulation tests, without priming with oestradiol. B) Turner syndrome: documented pre-established diagnosis by karyotype. Prepubertal status according to Tanner Pre-established history of normal thyroid function or adequate substitution for at least 3 months. Weight for stature within the population specific normal range (>5th and <95th percentiles) for gender Willingness and ability to comply with the protocol for the duration of the study. Parent's or guardian's written informed consent, given before any study related procedure that is not part of the subject's normal medical care, with the understanding that the subject or parent/guardian may withdraw consent at any time without prejudice to future medical care. If the child is old enough to read and write, a separate assent form will be given. Exclusion Criteria: Acquired GHD due to central nervous system tumour, trauma, infection, infiltration (documented by imaging), and history of irradiation or cranial surgery Previous treatment with GH, growth hormone-releasing hormone (GHRH), anabolic steroids or any treatment affecting growth. Previous treatment with corticosteroids, except in case of topical or inhaled corticosteroid administration for atopic disease. Corticosteroids for hormonal substitution are also allowed if the condition and the treatment regimen have been stable for at least 3 months. Severe associated pathology affecting growth such as malnutrition, malabsorption, or bone dysplasia. Chronic severe kidney disease. Chronic severe liver disease. Chronic infectious disease. Acute or severe illness during the previous 6 months. Significant concomitant illness that would interfere with participation or assessment in this study. Active malignancy (except non-melanomatous skin malignancies that have undergone surgical excision and/or biopsy, diagnosis and treatment to resolution) History or active Idiopathic intra-cranial hypertension (benign intracranial hypertension or pseudo-tumor cerebri). Diabetes Mellitus type I & II. Any autoimmune disease. Previous screening failure in this study. Use of an investigational drug or participation in another clinical study within the last three months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Local Medical Information Office
City
Buenos Aires
Country
Argentina
Facility Name
Local Medical Information Office
City
Sydney
Country
Australia
Facility Name
Local Medical Information Office
City
Vienna
Country
Austria
Facility Name
Local Medical Information Office
City
Mississauga
Country
Canada
Facility Name
Local Medical InformationOffice
City
Paris
Country
France
Facility Name
Local Medical Information Office
City
Munich
Country
Germany
Facility Name
Local Medical Information Office
City
Rome
Country
Italy
Facility Name
Local Medical Information Office
City
Oslo
Country
Norway
Facility Name
Local Medical Information Office
City
Russia
Country
Russian Federation
Facility Name
Local Medical Information Office
City
Singapore
Country
Singapore
Facility Name
Local Medical Information Office
City
Madrid
Country
Spain
Facility Name
Local Medical Information Office
City
Stockholm
Country
Sweden
Facility Name
Local Medical Information Office
City
Feltham
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23567489
Citation
Stevens A, Clayton P, Tato L, Yoo HW, Rodriguez-Arnao MD, Skorodok J, Ambler GR, Zignani M, Zieschang J, Della Corte G, Destenaves B, Champigneulle A, Raelson J, Chatelain P. Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome. Pharmacogenomics J. 2014 Feb;14(1):54-62. doi: 10.1038/tpj.2013.14. Epub 2013 Apr 9.
Results Reference
result
PubMed Identifier
34045667
Citation
Stevens A, Murray P, De Leonibus C, Garner T, Koledova E, Ambler G, Kapelari K, Binder G, Maghnie M, Zucchini S, Bashnina E, Skorodok J, Yeste D, Belgorosky A, Siguero JL, Coutant R, Vangsoy-Hansen E, Hagenas L, Dahlgren J, Deal C, Chatelain P, Clayton P. Gene expression signatures predict response to therapy with growth hormone. Pharmacogenomics J. 2021 Oct;21(5):594-607. doi: 10.1038/s41397-021-00237-5. Epub 2021 May 27.
Results Reference
derived
PubMed Identifier
29618660
Citation
Murray PG, Stevens A, De Leonibus C, Koledova E, Chatelain P, Clayton PE. Transcriptomics and machine learning predict diagnosis and severity of growth hormone deficiency. JCI Insight. 2018 Apr 5;3(7):e93247. doi: 10.1172/jci.insight.93247. eCollection 2018 Apr 5.
Results Reference
derived
PubMed Identifier
26340968
Citation
Valsesia A, Chatelain P, Stevens A, Peterkova VA, Belgorosky A, Maghnie M, Antoniazzi F, Koledova E, Wojcik J, Farmer P, Destenaves B, Clayton P; PREDICT Investigator group. GH deficiency status combined with GH receptor polymorphism affects response to GH in children. Eur J Endocrinol. 2015 Dec;173(6):777-89. doi: 10.1530/EJE-15-0474. Epub 2015 Sep 4.
Results Reference
derived
Links:
URL
http://www.saizenus.com
Description
Full FDA approved prescribing information can be found here

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Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®

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