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

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ClinicalTrials.gov Identifier: NCT01746862
Recruitment Status : Completed
First Posted : December 11, 2012
Results First Posted : October 18, 2016
Last Update Posted : October 18, 2016
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Tracking Information
First Submitted Date  ICMJE November 30, 2012
First Posted Date  ICMJE December 11, 2012
Results First Submitted Date  ICMJE August 24, 2016
Results First Posted Date  ICMJE October 18, 2016
Last Update Posted Date October 18, 2016
Study Start Date  ICMJE December 2012
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2016)
Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) Method [ Time Frame: Baseline, 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 7, 2012)
Change from baseline in growth velocity (centimeter/year [cm/yr]) at Month 6 [ Time Frame: Baseline, Month 6 ]
Change History Complete list of historical versions of study NCT01746862 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2016)
  • Change From Baseline in Height Velocity at Month 12 [ Time Frame: Baseline, 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 12 [ Time Frame: Baseline, Month 6, Month 12 ]
  • Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 12 [ Time Frame: Baseline, 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 12 [ Time Frame: Baseline, Month 6, Month 12 ]
  • 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 ]
  • 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) ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2012)
  • Change from baseline in growth velocity (cm/yr) at Month 12 [ Time Frame: Baseline, Month 12 ]
  • Changes from baseline in height (centimeter [cm]) at Month 6 and 12 [ Time Frame: Baseline, Month 6 and 12 ]
  • Changes from baseline in height standard deviation score (SDS) at Month 6 and 12 [ Time Frame: Baseline, Month 6 and 12 ]
  • 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 ]
  • Percentage of participants who adhered to study treatment [ Time Frame: Month 3, 6, 9 and 12 ]
  • Number of participants with adverse events (AEs) [ Time Frame: Baseline up to Month 13 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 3 Study to Evaluate the Safety and Efficacy of Saizen® in Children With Idiopathic Short Stature (ISS)
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Short Stature
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Saizen Test Group
    Intervention: Drug: Saizen®
  • Active Comparator: Saizen Control Group
    Intervention: Drug: Saizen®
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 1, 2014)
90
Original Estimated Enrollment  ICMJE
 (submitted: December 7, 2012)
87
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01746862
Other Study ID Numbers  ICMJE EMR200104-533
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck KGaA, Darmstadt, Germany
Study Sponsor  ICMJE Merck KGaA, Darmstadt, Germany
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Responsible Merck Ltd.
PRS Account Merck KGaA, Darmstadt, Germany
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP