Back to resultsA Phase 3 Study to Evaluate the Safety and Efficacy of Saizen® in Children With Idiopathic Short Stature (ISS)
Primary Purpose
Idiopathic Short Stature
Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Saizen®
Saizen®
Sponsored by
About this trial
This is an interventional treatment trial for Idiopathic Short Stature focused on measuring Saizen®, Recombinant human growth hormone (r-hGH), Idiopathic short stature, Height velocity, Bone age
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
Sites / Locations
- Please contact Merck KGaA Communication Center for Recruiting Sites
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Saizen Test Group
Saizen Control Group
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) Method
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
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
Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 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
Change From Baseline in Serum Concentration of Insulin Like Growth Factor Binding Protein-3 (IGFBP-3) at Month 6 and 12
Percentage of Adherence to Study Treatment
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
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.
Full Information
NCT ID
NCT01746862
First Posted
November 30, 2012
Last Updated
August 24, 2016
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01746862
Brief Title
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
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
December 2012 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
March 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Short Stature
Keywords
Saizen®, Recombinant human growth hormone (r-hGH), Idiopathic short stature, Height velocity, Bone age
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Saizen Test Group
Arm Type
Experimental
Arm Title
Saizen Control Group
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Saizen®
Other Intervention Name(s)
Somatropin, r-hGH
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Saizen®
Other Intervention Name(s)
Somatropin, r-hGH
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in Height Velocity at Month 6 Using Last Observation Carried Forward (LOCF) Method
Description
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.
Time Frame
Baseline, Month 6
Secondary Outcome Measure Information:
Title
Change From Baseline in Height Velocity at Month 12
Description
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.
Time Frame
Baseline, Month 12
Title
Change From Baseline in Height at Month 6 and 12
Time Frame
Baseline, Month 6, Month 12
Title
Change From Baseline in Height Standard Deviation Score (SDS) at Month 6 and 12
Description
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.
Time Frame
Baseline, Month 6, Month 12
Title
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
Title
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
Title
Percentage of Adherence to Study Treatment
Description
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.
Time Frame
6 months post-dose (Saizen Test Group and Saizen Control Group); 12 months post-dose (Saizen Test Group)
Title
Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs
Description
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.
Time Frame
Baseline up to Month 13
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Please contact Merck KGaA Communication Center for Recruiting Sites
City
Located in
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
30110706
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.
Results Reference
derived
Learn more about this trial
A Phase 3 Study to Evaluate the Safety and Efficacy of Saizen® in Children With Idiopathic Short Stature (ISS)
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