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

August 24, 2016 updated by: Merck KGaA, Darmstadt, Germany

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Located in, Korea, Republic of
        • Please contact Merck KGaA Communication Center for Recruiting Sites

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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
Active Comparator: Saizen Control 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
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, Month 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, Month 12
Change From Baseline in Height at Month 6 and 12
Time Frame: Baseline, Month 6, Month 12
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.
Baseline, Month 6, Month 12
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
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
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.
6 months post-dose (Saizen Test Group and Saizen Control Group); 12 months post-dose (Saizen Test 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.
Baseline up to Month 13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 18, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EMR200104-533

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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