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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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

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
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Change in percentage ejection fraction in subjects during the transition phase from childhood to adulthood

Secondary Outcome

 Subsidiary analysis of the other echocardiography parameters and lean body mass

Condition

Dwarfism

Intervention

r-hGH

Study Arms / Comparison Groups

 Group 1
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

34

Start Date

September 2003

Completion Date

February 2005

Primary Completion Date

February 2005

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
      

Gender

All

Ages

14 Years - 25 Years

Accepts Healthy Volunteers

No

Contacts

Theodor Wee, MD, , 



Administrative Informations


NCT ID

NCT01157793

Organization ID

IMP24632



Study Sponsor

Merck KGaA, Darmstadt, Germany


Study Sponsor

Theodor Wee, MD, Study Director, Merck Serono International SA


Verification Date

July 2010