A Phase 3 Study to Evaluate the Safety and Efficacy of Saizen® in Children With Idiopathic Short Stature (ISS)

• Change from baseline in growth velocity (cm/yr) at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
• Changes from baseline in height (centimeter [cm]) at Month 6 and 12 [ Time Frame: Baseline, Month 6 and 12 ] [ Designated as safety issue: No ]
• Changes from baseline in height standard deviation score (SDS) at Month 6 and 12 [ Time Frame: Baseline, Month 6 and 12 ] [ Designated as safety issue: No ]
• Changes from baseline in serum concentration of insulin-like growth factor-I (IGF-I) and insulin like growth factor binding protein-3 (IGFBP-3) at Month 6 and 12 [ Time Frame: Baseline, Month 3, 6, 9 and 12 ] [ Designated as safety issue: No ]
• Percentage of participants who adhered to study treatment [ Time Frame: Month 3, 6, 9 and 12 ] [ Designated as safety issue: No ]
• Number of participants with adverse events (AEs) [ Time Frame: Baseline up to Month 13 ] [ Designated as safety issue: Yes ]

This is an open-label, multi-center, randomized, two-arm parallel, no-treatment group controlled (only for the first 6 months), Phase 3 study in children with ISS. The subjects will be treated with 0.067 milligram/kilogram/day (mg/kg/day) of Saizen®, weight base dose, for 12 months (12 months of treatment in the test group, and 6 months of no treatment and then 6 months of treatment in the control group).

• Experimental: Saizen® treatment group
  Saizen® 0.067 mg/kg/day will be given for the duration of 12 months.
  Intervention: Drug: Saizen®
• Active Comparator: Control group
  For the first 6 months during the study no treatment will be given and for next 6 months Saizen® 0.067 mg/kg/day will be given.
  Intervention: Drug: Saizen®

Inclusion Criteria:

• Age greater than or equal to 5 years
• Pre-pubertal; testicular volume less than 4 milliliter (in males) and breast Stage 1 (in females)
• The official records of height (for example records measured in hospitals or schools) during previous 6 months or more preceding inclusion in the study (self-measurement of the height at home will not be considered as a valid record)
• Height less than or equal to 3rd percentile compared to same sex, same age
• Peak serum growth hormone (GH) greater than 10 microgram per liter (mcg/L) in GH stimulation test (results of peak serum GH greater than 10 mcg/L in GH stimulation test within 1 year can be used instead)
• Naive to GH therapy
• Normal birth weight (that is greater than or equal to 3rd percentile when compared to same sex)
• Normal thyroid function
• Normal karyotype in girls
• Written informed consent from parent/guardian
• Written informed consent from the subject who speaks, understand, read, and write Korean
• Bone age less than 10 years in boys and less than 9 years in girls, whose difference between the bone and chronological age is no more than 3 years

Exclusion Criteria:

• Puberty development (Tanner stage greater than or equal to 2)
• Skeletal dysplasia or abnormal body proportions
• Chronic systemic illness
• Dysmorphic syndrome
• Growth Hormone Deficiency
• Small for Gestational Age (SGA)
• Current medication for Attention deficit hyperactivity disorder (ADHD) or hyperactivity disorder
• Current medication with drugs that may influence secretion or action of growth hormone (such as estrogen, androgen, anabolic steroid, corticosteroid, thyroxine, aromatase inhibitors)
• Diabetes mellitus
• Kidney transplantation
• Acute critical illness, including complications following open heart surgery, abdominal surgery or multiple accidental trauma
• Acute respiratory failure
• Malignancy or previous therapy for malignancy
• Known hypersensitivity to somatotropin or any of its excipients including cresol or glycerol
• Closed epiphyses, progression or recurrence of an underlying intracranial tumor, chronic renal disease
• Endocrinologic or metabolic disorders such as Prader-Willi syndrome; Russel-Silver syndrome; Seckel syndrome; Down syndrome; Cushing syndrome; Noonan syndrome; short stature caused by other chromosomal abnormalities
• The disorders that explain short stature such as psychiatric disorders, nutritional disorders, and chronic debilitating diseases
• Participation in another clinical trial within the past 3 months
• Status of legal incapacity or limited legal capacity of the parents or legal guardian