Growth Hormone DeficiencyPhase 4NCT00256126
Predictive Markers in Growth Hormone Deficiency (GHD) and Turner Syndrome (TS) Children Treated With SAIZEN®
A Phase 4 study testing Saizen in people with Growth Hormone Deficiency and Turner Syndrome, run by Merck KGaA, Darmstadt, Germany at 13 sites in 13 countries.
Trial summary
The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children. Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Growth Hormone Deficiency, Turner Syndrome
- What is being tested?
- Saizen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 318 participants
- Where
- 13 sitesin 13 countries
- Study dates
- 31 May 2005to 30 Sep 2007
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- One of the following diagnoses and candidacy for SAIZEN® therapy:
- 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.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
13 sites in 13 countries.
13 sites in 13 countries
About this study
Official title: A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children Treated With SAIZEN®
The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children.
- Conditions
- Growth Hormone Deficiency, Turner Syndrome
- Being tested
- Saizen
- Medical subject headings
- Dwarfism, Pituitary, Turner Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaizenDrug
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
SaizenDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Turner Syndrome (TS) | Experimental | Not described Receives: Drug: Saizen |
| Growth Hormone Deficiency (GHD) | Experimental | Not described Receives: Drug: Saizen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Month 1
Secondary outcomes (5)
Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
Measured: Baseline, Month 1
Change From Baseline in Fasting Glucose Levels at Month 1
Measured: Baseline, Month 1
Change From Baseline in Fasting Insulin Levels at Month 1
Measured: Baseline, 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.
Measured: Baseline, Month 1
Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1
Measured: Baseline, Month 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2005 (estimated)
- Study start31 May 2005
- Primary completion30 Sep 2007
- Study completion30 Sep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Growth Hormone DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00256126
- Sponsor's protocol ID
- 24531
- Status last verified
- Mar 2018
- First submitted
- 18 Nov 2005
- Last updated
- 26 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 23567489Stevens 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.
PubMed 34045667Murray 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.
PubMed 29618660Valsesia 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.
PubMed 26340968
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IV Open-label Study of Predictive Markers in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children Treated With SAIZEN®
- ClinicalTrials.gov ID
- NCT00256126
- Acronym / sponsor ID
- 24531
- Conditions
- Growth Hormone Deficiency, Turner Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- 31 May 2005 (actual)
- Primary completion
- 30 Sep 2007 (actual)
- Study completion
- 30 Sep 2007 (actual)
- First posted
- 21 Nov 2005 (estimated)
- Results
- Posted 20 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims at identifying the predictive markers after one month of Saizen therapy in Growth Hormone Deficiency (GHD) and Turner Syndrome children.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Turner Syndrome (TS) | Experimental | Drug: Saizen |
| Growth Hormone Deficiency (GHD) | Experimental | Drug: Saizen |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- One of the following diagnoses and candidacy for SAIZEN® therapy:
- 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.
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SaizenSubjects 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 | Drug | Turner Syndrome (TS) |
| SaizenSubjects 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. | Drug | Growth Hormone Deficiency (GHD) |
Primary outcome
Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1
Time frame: 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.
5 secondary outcomes
Change From Baseline in Insulin-like Growth Factor Binding Protein - 3 (IGFBP-3) Level at Month 1
Time frame: Baseline, Month 1
Change From Baseline in Fasting Glucose Levels at Month 1
Time frame: Baseline, Month 1
Change From Baseline in Fasting Insulin Levels at Month 1
Time frame: Baseline, Month 1
Change From Baseline in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Month 1
Time frame: Baseline, Month 1
Change From Baseline in Bone Alkaline Phosphatase Levels at Month 1
Time frame: Baseline, Month 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23567489Stevens 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.
- Derived from this study: PubMed 34045667Stevens 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.
- Derived from this study: PubMed 29618660Murray 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.
- Derived from this study: PubMed 26340968Valsesia 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.
- Full FDA approved prescribing information can be found hereLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
Merck KGaA, Darmstadt, Germany
13 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Saizen in people with Growth Hormone Deficiency and Turner Syndrome, run by Merck KGaA, Darmstadt, Germany at 13 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Argentina, Australia, Austria, Canada, France and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Insulin Like Growth Factor-1 Standard Deviation Score (IGF-1 SDS) at Month 1 (time frame: Baseline, Month 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00256126, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2018.