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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01746862
First received: November 30, 2012
Last updated: August 24, 2016
Last verified: August 2016
  Purpose
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).

Condition Intervention Phase
Idiopathic Short Stature
Drug: Saizen®
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) Method [ Time Frame: Baseline, Month 6 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Height Velocity at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]
    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 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
    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 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Change From Baseline in Serum Concentration of Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) at Month 6 and 12 [ Time Frame: Baseline, Month 6, Month 12 ] [ Designated as safety issue: No ]
  • Percentage of Adherence to Study Treatment [ Time Frame: 6 months post-dose (Saizen Test Group and Saizen Control Group); 12 months post-dose (Saizen Test Group) ] [ Designated as safety issue: No ]
    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 TEAEs [ Time Frame: Baseline up to Month 13 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 90
Study Start Date: December 2012
Study Completion Date: March 2015
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Saizen Test Group Drug: Saizen®
Subjects in the Saizen test group will receive Saizen (recombinant-human growth hormone [r-hGH]) subcutaneously 6 days per week at a weight based dose of 0.067 milligram per kilogram of body weight per day (mg/kg/day) for 12 months.
Other Names:
  • Somatropin
  • r-hGH
Active Comparator: Saizen Control Group Drug: Saizen®
Subjects in the Saizen control group will receive no treatment for the first 6 months and thereafter will receive Saizen (r-hGH) subcutaneously 6 days per week at a weight based dose of 0.067 mg/kg/day for the next 6 months.
Other Names:
  • Somatropin
  • r-hGH

  Eligibility

Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746862

Locations
Korea, Republic of
Please contact Merck KGaA Communication Center for Recruiting Sites
Located in, Korea, Republic of
Sponsors and Collaborators
Merck KGaA
Investigators
Study Director: Medical Responsible Merck Ltd.
  More Information

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01746862     History of Changes
Other Study ID Numbers: EMR200104-533 
Study First Received: November 30, 2012
Results First Received: August 24, 2016
Last Updated: August 24, 2016
Health Authority: Korea: Food and Drug Administration
Korea: Institutional Review Board

Keywords provided by Merck KGaA:
Saizen®
Recombinant human growth hormone (r-hGH)
Idiopathic short stature
Height velocity
Bone age

Additional relevant MeSH terms:
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Endocrine System Diseases

ClinicalTrials.gov processed this record on December 08, 2016