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
Condition: Dwarfism; Growth Hormone Deficiency
MeSH terms: Dwarfism
Study type: Interventional
Phase: Phase 4

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
    

Intervention name(s): r-hGH; r-hGH
Intervention type(s): Drug; Drug
Intervention description(s): r-hGH at a dose of 0.15-1.00 mg/day administered for 48 weeks by s.c. route; 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 intervention name(s): Saizen®; Saizen®
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dwarfism; Growth hormone deficiency; Growth hormone