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

This study has been completed.
Sponsor:
Information provided by:
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01157793
First received: July 6, 2010
Last updated: July 9, 2014
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Dwarfism
Growth Hormone Deficiency
Drug: r-hGH
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Change in percentage ejection fraction in subjects during the transition phase from childhood to adulthood [ Time Frame: Baseline to study week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Subsidiary analysis of the other echocardiography parameters and lean body mass [ Time Frame: Baseline to study week 48 ] [ Designated as safety issue: No ]
  • Evaluation of laboratory parameters and monitoring of adverse events [ Time Frame: Baseline to study week 48 ] [ Designated as safety issue: Yes ]

Enrollment: 34
Study Start Date: September 2003
Study Completion Date: February 2005
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 Drug: r-hGH
r-hGH at a dose of 0.15-1.00 mg/day administered for 48 weeks by s.c. route
Other Name: Saizen®
Experimental: Group 2 Drug: r-hGH
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 Name: Saizen®

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
  Eligibility

Ages Eligible for Study:   14 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01157793

Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Theodor Wee, MD Merck Serono International SA
  More Information

No publications provided

Responsible Party: Sonia Shin, Head of Medical Department, Merck Serono Korea, an affiliate of MerckKGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT01157793     History of Changes
Other Study ID Numbers: IMP24632
Study First Received: July 6, 2010
Last Updated: July 9, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Merck KGaA:
Dwarfism
Growth hormone deficiency
Growth hormone

Additional relevant MeSH terms:
Dwarfism
Dwarfism, Pituitary
Endocrine System Diseases
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 15, 2014