- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01157793
A Multicentre, Randomised, Open-label, Controlled Study to Evaluate the Effects of Saizen® on Cardiac Function in Growth Hormone Deficient(GHD) Subjects During the Transition Phase From Childhood to Adulthood
A Multicentre, Randomised, Open-label, Controlled Study to Evaluate the Effects of Saizen® on Cardiac Function in GHD Subjects During the Transition Phase From Childhood to Adulthood
This was a 48-week, open-label, prospective, multicentric, randomised, comparative with parallel control, Phase 4 study to evaluate the effects of Saizen on cardiac function in GHD subjects during the transition phase from childhood to adulthood.
The study was designed to evaluate whether recombinant-human growth hormone (r-hGH) treatment also benefits young subjects with GHD. Some trials have already been published on this subject, but they were mainly focused on the bone density.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Growth hormone is a 191 amino acid polypeptide hormone (MW 22,000) normally synthesised and secreted by the somatotrophic cells of the anterior lobe of the pituitary gland. In normal development, growth hormone and somatomedins are responsible for many of the manifestations of normal growth and GHD is manifested by a marked short stature. Growth hormone deficiency has been treated by human growth hormone for many years. Serono's r-hGH (Saizen) is produced from genetically engineered mammalian cells.
The findings from previous clinical studies on GH treatment in GH-deficient adults, collectively indicate that the majority of adults with long-standing GH deficiency, whether dating from childhood or acquired in adult life, are compromised both physically and psychologically and can derive clinical benefit from GH replacement. Based on observations in the clinical trials to date , a GH dose of 0.01 mg/kg/day (50% of the dose used in children), is likely to be satisfactory for many subjects. Moreover, it should be possible to minimise early side effects, particularly fluid retention, by initiating treatment with half of this dose and increasing to the final dose after 4 weeks if well tolerated.
In this study, it was proposed to enroll a group of childhood onset GHD subjects who were not treated with r-hGH. Half of the study population started treatment for six months whilst the other half remained on no r-hGH treatment. After six months the group already on r-hGH therapy continued treatment for a further six months and the second group presently on no r-hGH treatment started r hGH treatment for the remaining six months of the study.
OBJECTIVES
Primary objective:
- To compare the effects of Saizen on cardiac function (as assessed by percentage ejection fraction) in subjects where 50% of the study population started r-hGH treatment for 24 weeks and then remained on r-hGH treatment for a further 24 weeks and subjects who continued on no r-hGH for 24 weeks before starting r-hGH for 24 weeks during the transition phase from childhood to adulthood.
Secondary objectives:
- To assess the safety and tolerability of r-hGH in subjects who were transitioning from childhood to adulthood, and to assess the change in body composition and lean body mass. Subsidiary analyses of the other echocardiography parameters was also performed.
After entry into the trial, the subjects were randomised to one of two groups for a 48-week period:
- Group 1: Saizen (r-hGH), 0.15-1.00 mg/day for 48 weeks, subcutaneous (s.c.)
- Group 2: No treatment for the first 24 weeks followed by Saizen (r-hGH)0.15-1.00 mg/day for the next 24 weeks, s.c.
Subjects' visits to the study site was scheduled as follows:
- Group 1 - Baseline (study day 1), weeks 4, 12, 24, 36 & 48.
- Group 2 - Baseline (study day 1), weeks 12, 24, 28, 36 & 48. The study drug was administered subcutaneously once daily in the evenings during the active treatment period. The dose was to be adjusted stepwise, controlled by Insulin-Growth Factor-I (IGF-I) values. The recommended final r-hGH dose was not to exceed 1.00mg/day
Study Type
Enrollment (Actual)
Phase
- Phase 4
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects with diagnosis of childhood onset GH deficiency and previously treated with GH
- Subjects who had attained final height
- Male or female subjects, aged between 14 and 25 years of age inclusively at baseline
- Subjects with GH deficiency of <5μg/L (acquired or idiopathic), established by any 1 type of GH secretion test within 3 years prior to Study Day 1
- If hypopituitary, subject must have been on adequate replacement therapy (if required) of glucocorticosteroids, thyroid & sex hormones (hormones levels on replacement being in normal/mildly elevated range) for at least 6 months prior to study entry
- Subjects who were willing and able to comply with the protocol for the duration of the study.
- Subjects who had given written informed consent before any study-related procedure not part of the subject's normal medical care, with the understanding that the subject might withdraw consent at any time without prejudice to future medical care
- Female subjects must be neither pregnant nor breast-feeding, and use a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Confirmation that a female subject was not pregnant was established by a negative urinary human chorionic gonadotropin (hCG) pregnancy test at baseline.
Exclusion Criteria:
- Subject who had a known allergy or hypersensitivity to growth hormone or diluent
- Subject who had been treated with r-hGH in previous six months
- Subject with chronic severe kidney disease
- Subject with chronic severe liver disease
- Subject with acute or severe illness during the previous 6 months
- Subject with significant concomitant illness which would interfere with his/her participation or assessment in this study
- Subject with active malignancy (except non-melanomatous skin malignancies)
- Subjects with unstable hypertension (supine systolic blood pressure persistently above 160 mmHg or diastolic blood pressure persistently above 100 mmHg)
- Subjects with benign cranial hypertension
- Subjects with a history of carpal tunnel syndrome, unless surgically released
- Subjects with known positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg) and/or Hepatitis C virus (HCV) serology based on past medical history
- Subjects with known active drug addiction, including alcoholism, or use of drugs for nontherapeutic purposes
- Subject who had previously participated in this study
- Subject taking an investigational drug or enrolled in another clinical study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 2
|
r-hGH at a dose of 0.15-1.00
mg/day administered for 48 weeks by s.c.
route
Other Names:
Initially no treatment for the first 24 weeks followed by administration of r-hGH at a dose of 0.15 1.00 mg/day for the next 24 weeks, by s.c.
route
Other Names:
|
Experimental: Group 1
|
r-hGH at a dose of 0.15-1.00
mg/day administered for 48 weeks by s.c.
route
Other Names:
Initially no treatment for the first 24 weeks followed by administration of r-hGH at a dose of 0.15 1.00 mg/day for the next 24 weeks, by s.c.
route
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in percentage ejection fraction in subjects during the transition phase from childhood to adulthood
Time Frame: Baseline to study week 48
|
Baseline to study week 48
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Subsidiary analysis of the other echocardiography parameters and lean body mass
Time Frame: Baseline to study week 48
|
Baseline to study week 48
|
Evaluation of laboratory parameters and monitoring of adverse events
Time Frame: Baseline to study week 48
|
Baseline to study week 48
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Theodor Wee, MD, Merck Serono International SA
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IMP24632
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Growth Hormone Deficiency
-
Novo Nordisk A/SCompletedGrowth Hormone Disorder | Adult Growth Hormone DeficiencyFrance
-
Novo Nordisk A/SCompletedGrowth Hormone Disorder | Adult Growth Hormone DeficiencyDenmark
-
Novo Nordisk A/SCompletedGrowth Hormone Disorder | Adult Growth Hormone DeficiencyGermany
-
Novo Nordisk A/SCompletedGrowth Hormone Disorder | Growth Hormone Deficiency in ChildrenIsrael, Denmark, Belgium, Spain, Macedonia, The Former Yugoslav Republic of, Turkey, United Kingdom, France, Slovenia, Czech Republic
-
Novo Nordisk A/SWithdrawnGrowth Hormone Disorder | Growth Hormone Deficiency in Children
-
Novo Nordisk A/SCompletedHealthy | Growth Hormone Disorder | Adult Growth Hormone DeficiencyUnited States
-
Teva Pharmaceutical Industries, Ltd.TerminatedGrowth Hormone-DeficiencyBelarus, Bulgaria, Georgia, Greece, Hungary, Israel, Poland, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine
-
OPKO Health, Inc.CompletedSafety and Efficacy Phase 2 Study of Long-acting hGH (MOD-4023) in Growth Hormone Deficient ChildrenPediatric Growth Hormone DeficiencyGreece, Hungary, Slovakia
-
Novo Nordisk A/SCompletedGrowth Hormone Disorder | Growth Hormone Deficiency in Children | Delivery SystemsGermany, Netherlands, Sweden
-
OPKO Health, Inc.CompletedAdult Growth Hormone DeficiencyCzechia, Hungary, Israel, Serbia, Slovakia, Slovenia
Clinical Trials on r-hGH
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EMD SeronoCompletedGrowth Hormone Deficiency | Growth FailureGermany
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Merck KGaA, Darmstadt, GermanyCompleted
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Merck KGaA, Darmstadt, GermanyCompletedIdiopathic Short StatureKorea, Republic of
-
EMD SeronoTerminatedGrowth Hormone Deficiency (GHD)United States
-
Merck KGaA, Darmstadt, GermanyMerck Serono S.A., GenevaCompletedChildren Born With Serious Intra-uterine Growth Retardation
-
Teva Neuroscience, Inc.Teva Branded Pharmaceutical Products R&D, Inc.; TransPharma MedicalCompleted
-
Visen Pharmaceuticals (Shanghai) Co., Ltd.Ascendis Pharma A/SUnknownEndocrine System Diseases | Pituitary Diseases | Growth Hormone Deficiency | Hormones | Pituitary Disease, AnteriorChina
-
Merck KGaA, Darmstadt, GermanyMerck Serono S.P.A., ItalyTerminated
-
EMD SeronoCompletedHIV Infections | HIV Wasting Syndrome
-
EMD SeronoCompletedHuman Immunodeficiency Virus Infections | Human Immunodeficiency Virus-associated Adipose Redistribution Syndrome (HARS)