Growth Hormone Deficiency, Turner Syndrome
Conditions
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.
Interventions
DRUGSaizen
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
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1 | Baseline, 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1 | Baseline, Month 1 | — |
| Change From Baseline in Fasting Glucose Levels at Month 1 | Baseline, Month 1 | — |
| Change From Baseline in Fasting Insulin Levels at Month 1 | Baseline, Month 1 | — |
| Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1 | Baseline, 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 | Baseline, Month 1 | — |
Countries
Argentina, Australia, Austria, Canada, France, Germany, Italy, Norway, Russia, Singapore, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
First informed consent date: May 2005. Clinical data cutoff date: Oct 2007, Study completion date: Sep 2007.
Pre-assignment details
A total of 319 subjects were screened for this trial. Only 1 subject withdrew from the study prior to receiving the treatment due to personal reasons. Overall, 318 subjects were enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| Turner Syndrome (TS) Subjects with TS were administered with 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. | 149 |
| Growth Hormone Deficiency (GHD) Subjects with GHD were administered with 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. | 169 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Other | 1 | 2 |
Baseline characteristics
| Characteristic | Turner Syndrome (TS) | Growth Hormone Deficiency (GHD) | Total |
|---|---|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 4.08 | 8.94 years STANDARD_DEVIATION 3.17 | 9.11 years STANDARD_DEVIATION 3.62 |
| Sex: Female, Male Female | 149 Participants | 63 Participants | 212 Participants |
| Sex: Female, Male Male | 0 Participants | 106 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 149 | 51 / 169 |
| serious Total, serious adverse events | 0 / 149 | 1 / 169 |
Outcome results
Primary
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.
Time frame: Baseline, Month 1
Population: The Intention to Treat (ITT) population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1 | 1.7692 Standard deviation score (SDS) | Standard Deviation 1.1889 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1 | 1.4007 Standard deviation score (SDS) | Standard Deviation 0.9811 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1
Time frame: Baseline, Month 1
Population: The ITT population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1 | 21.13 Units per liter (U/L) | Standard Deviation 80.68 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1 | 14.78 Units per liter (U/L) | Standard Deviation 25.23 |
Secondary
Change From Baseline in Fasting Glucose Levels at Month 1
Time frame: Baseline, Month 1
Population: The ITT population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Fasting Glucose Levels at Month 1 | 0.22 millimoles per liter (mmol/L) | Standard Deviation 0.8 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Fasting Glucose Levels at Month 1 | 0.13 millimoles per liter (mmol/L) | Standard Deviation 0.65 |
Secondary
Change From Baseline in Fasting Insulin Levels at Month 1
Time frame: Baseline, Month 1
Population: The ITT population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Fasting Insulin Levels at Month 1 | 47.7 picomole per liter (pmol/L) | Standard Deviation 177.2 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Fasting Insulin Levels at Month 1 | 26.9 picomole per liter (pmol/L) | Standard Deviation 79.8 |
Secondary
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.
Time frame: Baseline, Month 1
Population: The ITT population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1 | 2.132 picomole per liter *millimole per liter | Standard Deviation 10.296 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1 | 1.061 picomole per liter *millimole per liter | Standard Deviation 3.885 |
Secondary
Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
Time frame: Baseline, Month 1
Population: The ITT population included all subjects who received at least 1 dose of study medication. Here Overall Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Turner Syndrome (TS) | Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1 | 0.86 milligram per liter (mg/L) | Standard Deviation 0.96 |
| Growth Hormone Deficiency (GHD) | Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1 | 0.69 milligram per liter (mg/L) | Standard Deviation 0.81 |