Clinical trial NCT01746862: A Phase 3 Study to Evaluate the Safety and Efficacy of Saizen® in Children With Idiopathic Short Stature (ISS)
Official title: A Randomized, Open-label, Two-arm Parallel Group, No Treatment Group-controlled, Multicenter Phase III Study to Evaluate the Safety and Efficacy of Saizen® 0.067 mg/kg/Day Subcutaneous Injection in Children With Idiopathic Short Stature
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Idiopathic Short Stature
Keywords: Saizen®
Recombinant human growth hormone (r-hGH)
Idiopathic short stature
Height velocity
Bone age
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2012-12-11
Enrollment: 90
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) Method
timeFrame: Baseline, Month 6
Secondary outcomes:
measure: Change From Baseline in Height Velocity at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Height at Month 6 and 12
timeFrame: Baseline, Month 6, Month 12
measure: Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 12
timeFrame: Baseline, Month 6, Month 12
measure: Change From Baseline in Serum Concentration of Insulin-like Growth Factor-I (IGF-I) at Month 6 and 12
timeFrame: Baseline, Month 6, Month 12
measure: Change From Baseline in Serum Concentration of Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) at Month 6 and 12
timeFrame: Baseline, Month 6, Month 12
measure: Percentage of Adherence to Study Treatment
timeFrame: 6 months post-dose (Saizen Test Group and Saizen Control Group); 12 months post-dose (Saizen Test Group)
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs
timeFrame: Baseline up to Month 13
Other outcomes:
Locations:
city: Located in
country: Korea, Republic of
facility: Please contact Merck KGaA Communication Center for Recruiting Sites
Study officials:
affiliation: Merck Ltd.
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Chung WY, Yoo HW, Hwang JS, Ko CW, Kim HS, Jin DK, Lee KH, Han HS, Paranchothy P, Suh BK. Effect of Growth Hormone Therapy on Height Velocity in Korean Children with Idiopathic Short Stature: A Phase III Randomised Controlled Trial. Horm Res Paediatr. 2018;90(1):44-53. doi: 10.1159/000491016. Epub 2018 Aug 15.