search
Back to results

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
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dwarfism focused on measuring Dwarfism, Growth hormone deficiency, Growth hormone

Eligibility Criteria

14 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    July 6, 2010
    Last Updated
    July 9, 2014
    Sponsor
    Merck KGaA, Darmstadt, Germany
    search

    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

    We'll reach out to this number within 24 hrs