Back to resultsTreatment of Children and Adolescents With Growth Failure Associated With Primary IGF-1 Deficiency
Primary Purpose
Growth Disorders
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
rh IGF-1 (mecasermin)
Sponsored by
About this trial
This is an interventional treatment trial for Growth Disorders focused on measuring Insulin-like Growth Factor Deficiency, IGF-1, Short Stature
Eligibility Criteria
Inclusion Criteria: Parents or legally authorized representatives must give signed informed consent before any trial related activities are conducted Where required, assent of the subject will be appropriately documented prior to any study related activities Completion of assessments at Visit 9 (Month 120 of Study MS301 [NCT00125164]) Exclusion Criteria: Incomplete participation in MS301 (NCT00125164) Known or suspected allergy to the trial product (mecasermin, recombinant human IGF-1 injection) or its formulation Development or presence of a chronic condition except as approved by the Medical Monitor Pregnancy Any social or medical condition that, in the opinion of the investigator, would be detrimental to either the subject or the study
Sites / Locations
- Ipsen
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All rhIGF-1 Subjects
Arm Description
All subjects entering MS306 began recombinant human insulin-like growth factor-1 (rhIGF-1) twice a day (BID) treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 micrograms [μg]/ kilogram [kg] BID). MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID. Following Protocol Amendment 1, all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2. Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 once a day (QD), followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study.
Outcomes
Primary Outcome Measures
Height Velocity During BID Dosing Period
Height was measured standing, without shoes, as the average of 3 measurements by the same observer identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height velocity (during any interval of time (annualised) is computed as (height on date 2 - height on date 1)/(age on date 2 - age on date 1) where height is expressed as centimetres so that height velocity is expressed as centimetres per year (cm/yr). Height velocity is presented for subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Secondary Outcome Measures
Mean Change From Baseline in Height Standard Deviation (SD) Score During BID Dosing Period
Height was measured standing, without shoes, as the average of 3 measurements by the same observer using identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height SD score was determined using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in height SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Mean Change From Baseline in Body Mass Index (BMI) SD Score During BID Dosing Period
BMI SD score was calculated using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in BMI SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Mean Change From Baseline in Bone Age During BID Dosing Period
Radiographs of the left hand and wrist were taken on an approximately annual basis for determination of bone (skeletal) age. The films were sent to a central facility for standardised evaluation. Mean change from baseline in bone age is presented for all subjects completing each year of BID treatment (i.e. Year1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Mean Change From Baseline in Predicted Adult Height During BID Dosing Period
Predicted adult heights were estimated using the Roche-Wainer-Theissen method which takes into account changes in age, height and bone age. Mean change from baseline in predicted adult height is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00330668
Brief Title
Treatment of Children and Adolescents With Growth Failure Associated With Primary IGF-1 Deficiency
Official Title
Recombinant Human Insulin-Like Growth Factor-1 (IGF-1) Treatment of Children With Growth Failure Associated With Primary IGF-1 Deficiency: An Open-Label, Multi-Center, Extension Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Terminated
Why Stopped
Unacceptable frequency of hypoglycemia observed at and above 200 ug/kg/day
Study Start Date
November 2005 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
March 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an extension study to Tercica study MS301 (NCT00125164) and is intended to collect long term safety and efficacy data on the continued use of recombinant human insulin-like growth factor-1 (rh IGF-1) in children and adolescents treated for primary IGF-1 deficiency (IGFD). The secondary objective is to use the data collected to learn more about the relationship of IGF-1 exposure to the promotion of normal growth and pubertal development.
Detailed Description
Primary IGFD is a term that has been used to describe patients with intrinsic cellular defects in GH action. In this protocol, subjects that have completed one year of mecasermin treatment on Tercica protocol MS301 (NCT00125164) will be allowed to enroll in this extension study. All subjects were planned to receive treatment.
This is a Phase IIIb open-label, multi-center, parallel dose, extension study conducted in approximately 40 centers across the United States.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Growth Disorders
Keywords
Insulin-like Growth Factor Deficiency, IGF-1, Short Stature
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
114 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All rhIGF-1 Subjects
Arm Type
Experimental
Arm Description
All subjects entering MS306 began recombinant human insulin-like growth factor-1 (rhIGF-1) twice a day (BID) treatment. Each subject treated in MS301 had an MS306 starting dose that was based on their dose at the completion of MS301 (i.e. subcutaneous injections of rhIGF-1 at 40, 80, or 120 micrograms [μg]/ kilogram [kg] BID).
MS301 untreated control subjects were randomised in MS306 in a 1:1 ratio to a dose of either 80 or 120 μg/kg rhIGF-1 BID.
Following Protocol Amendment 1, all subjects received either 80 or 120 μg/kg rhIGF-1 BID until the implementation of Protocol Amendment 2.
Following Protocol Amendment 2, all subjects were first switched to receive subcutaneous injections of 160 μg/kg rhIGF-1 once a day (QD), followed by individual dose-escalation first to 200 μg/kg rhIGF-1 QD and subsequently to a targeted maximum dose of 240 μg/kg rhIGF-1 QD. Subjects were treated QD until the early termination of the study.
Intervention Type
Drug
Intervention Name(s)
rh IGF-1 (mecasermin)
Other Intervention Name(s)
Increlex
Intervention Description
Patients from untreated arm for prior study MS301 (NCT00125164) were randomized to a dose of either 80 or 120 mcg/kg twice daily. For patients receiving active treatment in previous study MS 301 (NCT00125164), they started on a dose of 80 or 120 mcg/kg twice daily based on the dose reached at end of the previous study. Following a protocol amendment in May 2009, all patients were switched to once daily doses of 160 µg/kg, escalated to a targeted maximum dose of 240 µg/kg.
Primary Outcome Measure Information:
Title
Height Velocity During BID Dosing Period
Description
Height was measured standing, without shoes, as the average of 3 measurements by the same observer identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height velocity (during any interval of time (annualised) is computed as (height on date 2 - height on date 1)/(age on date 2 - age on date 1) where height is expressed as centimetres so that height velocity is expressed as centimetres per year (cm/yr). Height velocity is presented for subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Time Frame
At Years 1, 2 and 3 in BID dosing period.
Secondary Outcome Measure Information:
Title
Mean Change From Baseline in Height Standard Deviation (SD) Score During BID Dosing Period
Description
Height was measured standing, without shoes, as the average of 3 measurements by the same observer using identical technique with a Harpenden or other wall-mounted stadiometer at baseline and each study visit up to 3 years. Height SD score was determined using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in height SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Time Frame
At baseline and Years 1, 2 and 3 in BID dosing period.
Title
Mean Change From Baseline in Body Mass Index (BMI) SD Score During BID Dosing Period
Description
BMI SD score was calculated using the National Center for Health Statistics 2000 data as provided by the Center for Disease Control. The SD score was calculated as the patient value minus the mean divided by the standard deviation. The mean and the standard deviation vary depending on the age and sex of the child. Mean change from baseline in BMI SD score is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Time Frame
At baseline and Years 1, 2 and 3 in BID dosing period.
Title
Mean Change From Baseline in Bone Age During BID Dosing Period
Description
Radiographs of the left hand and wrist were taken on an approximately annual basis for determination of bone (skeletal) age. The films were sent to a central facility for standardised evaluation. Mean change from baseline in bone age is presented for all subjects completing each year of BID treatment (i.e. Year1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Time Frame
At baseline and Years 1, 2 and 3 in BID dosing period.
Title
Mean Change From Baseline in Predicted Adult Height During BID Dosing Period
Description
Predicted adult heights were estimated using the Roche-Wainer-Theissen method which takes into account changes in age, height and bone age. Mean change from baseline in predicted adult height is presented for all subjects completing each year of BID treatment (i.e. Year 1 [0-1 years], Year 2 [1-2 years], Year 3 [2-3 years]).
Time Frame
At baseline and Years 1, 2 and 3 in BID dosing period.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Parents or legally authorized representatives must give signed informed consent before any trial related activities are conducted
Where required, assent of the subject will be appropriately documented prior to any study related activities
Completion of assessments at Visit 9 (Month 120 of Study MS301 [NCT00125164])
Exclusion Criteria:
Incomplete participation in MS301 (NCT00125164)
Known or suspected allergy to the trial product (mecasermin, recombinant human IGF-1 injection) or its formulation
Development or presence of a chronic condition except as approved by the Medical Monitor
Pregnancy
Any social or medical condition that, in the opinion of the investigator, would be detrimental to either the subject or the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sr Vice President, Clinical Development and Medical Affairs
Organizational Affiliation
Ipsen (formerly Tercica, Inc.)
Official's Role
Study Director
Facility Information:
Facility Name
Ipsen
City
Paris
Country
France
12. IPD Sharing Statement
Learn more about this trial
Treatment of Children and Adolescents With Growth Failure Associated With Primary IGF-1 Deficiency
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