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

Condition(s) targeted: Childhood-Onset Growth Hormone Deficiency; Pituitary Dwarfism

Intervention: Saizen® (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: EMD Serono

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.

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 design: Treatment, Randomized, Open Label, Dose Comparison, Single Group Assignment, Efficacy Study

Primary outcome: Increase in percent of trunk fat in COGHD

Secondary outcome: Changes in lean body mass and body composition parameters

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 21 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 30 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, IGF-I, IGFBP-3, free T4 , total T4, 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.

Minimum age: 13 Years. Maximum age: 21 Years. Gender(s): Both.

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 21 years of age, inclusive

- Diagnosis of childhood onset GH deficiency and prior completed 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 SD1.

- 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) within the past 6 months.

- 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 study entry.

- 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 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 study entry.

- 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.

Children’s Hospital of Orange County, Orange, California 92868, United States

Pediatric Endocrinology Children’s Clinic, Tallahassee, Florida 32308, United States

Nemours Children’s Clinic, Orlando, Florida 32806, United States

Nemours Children’s Clinic, Jacksonville, Florida 32226, United States

Pediatric Endocrine Associates, Atlanta, Georgia 30342, United States

Women’s and Children’s Hospital of Buffalo, Buffalo, New York 14222, United States

Columbia University, New York, New York 10032, United States

Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Children’s Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States

Full FDA approved prescribing information can be found here

Starting date: August 2004
Ending date: July 2006
Last updated: June 11, 2007