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
Primary Purpose
Dwarfism, Growth Hormone Deficiency
Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
r-hGH
r-hGH
Sponsored by
About this trial
This is an interventional treatment trial for Dwarfism focused on measuring Dwarfism, Growth hormone deficiency, Growth hormone
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1
Group 2
Arm Description
Outcomes
Primary Outcome Measures
Change in percentage ejection fraction in subjects during the transition phase from childhood to adulthood
Secondary Outcome Measures
Subsidiary analysis of the other echocardiography parameters and lean body mass
Evaluation of laboratory parameters and monitoring of adverse events
Full Information
NCT ID
NCT01157793
First Posted
July 6, 2010
Last Updated
July 9, 2014
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01157793
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2010
Overall Recruitment Status
Completed
Study Start Date
September 2003 (undefined)
Primary Completion Date
February 2005 (Actual)
Study Completion Date
February 2005 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dwarfism, Growth Hormone Deficiency
Keywords
Dwarfism, Growth hormone deficiency, Growth hormone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
34 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1
Arm Type
Experimental
Arm Title
Group 2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
r-hGH
Other Intervention Name(s)
Saizen®
Intervention Description
r-hGH at a dose of 0.15-1.00 mg/day administered for 48 weeks by s.c. route
Intervention Type
Drug
Intervention Name(s)
r-hGH
Other Intervention Name(s)
Saizen®
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in percentage ejection fraction in subjects during the transition phase from childhood to adulthood
Time Frame
Baseline to study week 48
Secondary Outcome Measure Information:
Title
Subsidiary analysis of the other echocardiography parameters and lean body mass
Time Frame
Baseline to study week 48
Title
Evaluation of laboratory parameters and monitoring of adverse events
Time Frame
Baseline to study week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theodor Wee, MD
Organizational Affiliation
Merck Serono International SA
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
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
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