Cool.Click™ Adolescent Transition Study: Study of Saizen® in Subjects With Childhood-onset Growth Hormone Deficiency

Pituitary Dwarfism Clinical Trial

Official title:

A Phase IIIb, Prospective, Multicenter, Randomized, Open-label Study to Determine the Safety and Efficacy of Two Different Dosing Regimens of Saizen® (Recombinant Human Growth Hormone (r-hGH), Using Cool.Click™ in Subjects With Childhood-onset Growth Hormone Deficiency During the Adolescent Transition Phase (CATS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00109733
• Other study ID #: 25253
• Status: Completed
• Phase: Phase 3
• First received: May 2, 2005
• Last updated: August 4, 2013
• Start date: January 2005
• Est. completion date: July 2006

Study information

• Verified date: August 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective is to evaluate the efficacy and safety of two different dose regimens of r-hGH (Saizen®) in subjects with childhood-onset growth hormone deficiency (COGHD) during the transition phase from childhood to adulthood.

Description:

This is a phase IIIb, prospective, multicenter, randomised, open label study to determine the safety and efficacy of two different dose regimens of r-hGH with a dose escalation scheme. Screening assessments must be completed 30 days prior to SD1 (Study Day 1). Eligible subjects ages 13 to 25 years will be randomised in equal allocation in a 1:1 ratio to one of two treatment groups (30 subjects/group). Daily subcutaneous injections will be self-administered or received from a designated individual using cool.click™, the needle-free growth hormone (GH) delivery device. The study consists of three periods: screening (up to 30 days prior to Study Day 1), active treatment (up to 24 weeks), and follow-up (4 week safety evaluation after the last dose of study medication).

Each subject will be required to complete a daily treatment diary to assess dosing compliance, adverse events, and concomitant medications. Each subject will receive one treatment diary at SD1, weeks 8, 12, and 24. Subjects will be required to record daily diary entries that will capture dosing compliance, adverse events, and concomitant medications. Depending upon treatment allocation and subject tolerability, dose titration will be increased as follows:

• Group A: 0.005 mg/kg/day for 30 days then increasing, with the Investigator's approval, to 0.010 mg/kg/day from day 31 to week 24.

• Group B: 0.010 mg/kg/day for 14 days with the opportunity to dose escalate, with the Investigator's approval, on day 15 to 0.02 mg/kg/day and day 29 to 0.03 mg/kg/day.

Scheduled study visits include screening, baseline, and weeks 8, 12, and 24. Dosage adjustments will be based on subject tolerability and telephone assessments from study drug initiation through week 6. Trunk fat will be measured at SD1, weeks 12 and 24 (or early termination visit). Routine clinical laboratory assessments (hematology, blood chemistries, and urinalysis) will be performed pre-treatment (-30 to -1 SD1) and post-treatment on week 24 (or early termination visit). Special laboratory assessments include the central analysis of lipid panel, fasting insulin, fasting glucose, insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), free thyroxine (T4) , total T4, C-reactive protein (CRP). Physical exams will be performed at screening, weeks 12 and 24. Safety evaluations will occur during scheduled study visits, through telephone assessments, and by the review of adverse events and concomitant events on the subject treatment diary.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: July 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years to 25 Years

Eligibility

Inclusion Criteria:

The day of entry or Study Day 1 is defined as the first day of study treatment. To be eligible for inclusion into this study, the subjects must fulfill all of the following criteria within 30 days prior to Study Day 1.

• Male or female from 13 to 25 years of age, inclusive

• Diagnosis of childhood onset growth hormone deficiency (GHD) and prior completed growth hormone (GH) treatment as evidenced by bone age greater than 14 years for girls and 16 years for boys or no height increase > 0.5 cm in the 6 months prior to Screen.

• Have documented GH deficiency (acquired or idiopathic), established by a standard provocative test, such as insulin (<5 ng/mL) or growth hormone releasing hormone plus arginine (<9 ng/mL) at least 30 days after GH has been discontinued. If a subject is hypopituitary with two or more pituitary disorders and has a low IGF-1, the stimulation test does not need to be performed to confirm GHD.

• If hypopituitary, must have been on adequate replacement therapy (if required) of glucocorticosteroids, thyroid and sex hormones (hormone levels on replacement being in normal/mildly elevated range) for at least 6 months prior to Screen.

• Be willing and able to comply with the protocol for the duration of the study.

• Have given written informed consent before any study-related procedure not part of the subject's normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.

• Female subjects of childbearing potential must use a hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Confirmation that a female patient is not pregnant must be established by a negative human chorionic gonadotrophin (hCG) pregnancy test (urine or serum) within 7 days of study enrolment (SD1).

Exclusion Criteria:

To be eligible for inclusion in this study the subjects must not meet any of the following criteria:

• Known allergy or hypersensitivity to growth hormone or diluent.

• Previous treatment with GH within six months prior to Screen.

• Severe illness during the previous six months.

• Active malignancy (except non-melanomatous skin malignancies).

• Diabetes mellitus (type I or II).

• Seropositivity for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg) and/or Hepatitis C Virus (HCV) serology.

• Pregnancy or lactation.

• History of drug and/or alcohol abuse or use of drugs for non-therapeutic purposes.

• Any medical condition that, in the opinion of the Investigator, would jeopardize the patient's safety following exposure to study drug.

• Clinically significant abnormal hematology, chemistry or urinalysis results at screening in the judgment of the Investigator.

• Have taken another investigational drug or had any experimental procedure in the six months preceding study entry.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood-onset Growth Hormone Deficiency
• Dwarfism, Pituitary
• Endocrine System Diseases
• Pituitary Dwarfism

Intervention

Biological:
• recombinant human growth hormone
0.005 mg/kg/day for 30 days then increasing, with the Investigator's approval, to 0.010 mg/kg/day from Day 31 to Week 24.
• recombinant human growth hormone
0.010 mg/kg/day for 14 days with the opportunity to dose escalate, with the Investigator's approval, on Day 15 to 0.02 mg/kg/day and Day 29 to 0.03 mg/kg/day.

Locations

Country	Name	City	State
United States	Pediatric Endocrine Associates	Atlanta	Georgia
United States	Women's and Children's Hospital of Buffalo	Buffalo	New York
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University	New York	New York
United States	Children's Hospital of Orange County	Orange	California
United States	Nemours Children's Clinic	Orlando	Florida
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Pediatric Endocrinology Children's Clinic	Tallahassee	Florida

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 24 in Trunk Fat		Baseline to Week 24	No
Secondary	Percent Change From Baseline to Week 24 in Lean Body Mass		Baseline to Week 24	No
Secondary	Percent Change From Baseline to Week 24 in Total Body Fat		Baseline to Week 24	No
Secondary	Percent Change From Baseline to Week 24 in Limb Fat		Baseline to Week 24	No
Secondary	Percent Change From Baseline to Week 24 in Trunk to Limb Fat Ratio		Baseline to Week 24	No

External Links

•   Full FDA approved prescribing information can be found here