Clinical trial NCT00109733: Cool.Click™ Adolescent Transition Study: Study of Saizen® in Subjects With Childhood-onset Growth Hormone Deficiency
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Childhood-onset Growth Hormone Deficiency
Pituitary Dwarfism
Keywords: Childhood-onset growth hormone deficiency (COGHD)
Saizen®
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2005-05-03
Enrollment: 31
Sex: ALL
Minimum age (years): 13
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline to Week 24 in Trunk Fat
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Percent Change From Baseline to Week 24 in Lean Body Mass
timeFrame: Baseline to Week 24
measure: Percent Change From Baseline to Week 24 in Total Body Fat
timeFrame: Baseline to Week 24
measure: Percent Change From Baseline to Week 24 in Limb Fat
timeFrame: Baseline to Week 24
measure: Percent Change From Baseline to Week 24 in Trunk to Limb Fat Ratio
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Tallahassee
country: United States
facility: Pediatric Endocrinology Children's Clinic
state: Florida
city: Atlanta
country: United States
facility: Pediatric Endocrine Associates
state: Georgia
city: Buffalo
country: United States
facility: Women's and Children's Hospital of Buffalo
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: EMD Serono
name: Sanja Dragnic, MD
role: STUDY_DIRECTOR
References: