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

Phase 3
Completed
Conditions
Idiopathic Short Stature
Interventions
Registration Number
NCT01746862
Lead Sponsor
Merck KGaA, Darmstadt, Germany
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
90
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Saizen Control GroupSaizen®-
Saizen Test GroupSaizen®-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) MethodBaseline, Month 6

Baseline height is defined as the last available height measurement before randomization. Baseline height velocity = (\[Baseline height minus height measurement obtained at least 6 months prior\] / 6) \* 12. Height velocity at Month 6 = (\[Month 6 height minus height measurement obtained at least 6 months prior\] / 6) \* 12.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Height Velocity at Month 12Baseline, Month 12

Baseline height is defined as the last available height measurement before randomization. Baseline height velocity = (\[Baseline height minus height measurement obtained at least 12 months prior\] / 12) \* 12. Height velocity at Month 12 = (\[Month 12 height minus height measurement obtained at least 12 months prior\] / 12) \* 12.

Change From Baseline in Height at Month 6 and 12Baseline, Month 6, Month 12
Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 12Baseline, Month 6, Month 12

Height SDS was calculated as: Height SDS = (measured height - population mean) / population standard deviation, where mean and standard deviation were based on the Korean standard growth charts. SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) a subject's value was relative to the mean of the reference population. The scores were centred around zero. Negative score indicated a subject was smaller for their age/gender.

Change From Baseline in Serum Concentration of Insulin-like Growth Factor-I (IGF-I) at Month 6 and 12Baseline, Month 6, Month 12
Change From Baseline in Serum Concentration of Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) at Month 6 and 12Baseline, Month 6, Month 12
Percentage of Adherence to Study Treatment6 months post-dose (Saizen Test Group and Saizen Control Group); 12 months post-dose (Saizen Test Group)

Percentage of adherence to study treatment (adherence rate) was defined as the actual number of received treatments divided by the scheduled number of treatments multiplied by 100. The adherence rate for 6 months was calculated from Baseline to 6 months for the Saizen Test Group and from Month 6 to Month 12 for the Saizen Control Group.

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEsBaseline up to Month 13

An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. For the Saizen Test Group, TEAEs were defined as events that occurred or worsened at or after the first administration of treatment and for the Saizen Control Group, TEAEs were defined as events that occurred or worsened at or after the randomization.

Trial Locations

Locations (1)

Please contact Merck KGaA Communication Center for Recruiting Sites

🇰🇷

Located in, Korea, Republic of

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