Growth DisordersPhase 3NCT00330668

Treatment of Children and Adolescents With Growth Failure Associated With Primary IGF-1 Deficiency

A Phase 3 study testing rh IGF-1 (mecasermin) in people with Growth Disorders, run by Ipsen at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 4 to 15 years
Conditions the study is for: Growth Disorders
What is being tested?: rh IGF-1 (mecasermin)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 114 participants
Where: 1 siteFrance
Study dates: Nov 2005to Mar 2010
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 4 to 15 years
All sexes
No healthy volunteers
Child

Who may be able to join

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])

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

France1 site

Ipsen
Paris

Other trials in France

About this study

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

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.

Read the 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.

Conditions: Growth Disorders
Being tested: rh IGF-1 (mecasermin)
Keywords: Insulin-like Growth Factor Deficiency, IGF-1, Short Stature
Medical subject headings: Growth Disorders, Dwarfism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

rh IGF-1 (mecasermin)Drug
Also called Increlex
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.

Study groups in NCT00330668
Study group	Role	What they receive
All rhIGF-1 Subjects	Experimental	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. Receives: Drug: rh IGF-1 (mecasermin)

What is being measured

The primary outcome is the main question the study is designed to answer.

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]).
Measured: At Years 1, 2 and 3 in BID dosing period.

Secondary outcomes (4)

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]).
Measured: At baseline and Years 1, 2 and 3 in BID dosing period.
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]).
Measured: At baseline and Years 1, 2 and 3 in BID dosing period.
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]).
Measured: At baseline and Years 1, 2 and 3 in BID dosing period.
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]).
Measured: At baseline and Years 1, 2 and 3 in BID dosing period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2005Mar 2010

First posted29 May 2006 (estimated)
Study startNov 2005
Primary completionFeb 2010
Study completionMar 2010

Why it stopped: Unacceptable frequency of hypoglycemia observed at and above 200 ug/kg/day

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Growth DisordersStudies of the same condition, open and under way.
More trials run by IpsenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 114 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00330668
Sponsor's protocol ID: MS306
Other IDs: 2019-000844-81, 2019
Status last verified: Aug 2020
First submitted: 26 May 2006
Last updated: 14 Aug 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00330668
Acronym / sponsor ID: MS306
Conditions: Growth Disorders
Keywords: Insulin-like Growth Factor Deficiency, IGF-1, Short Stature
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Unacceptable frequency of hypoglycemia observed at and above 200 ug/kg/day
Enrolment: 114 participants (actual)
Lead sponsor: IpsenIndustry (pharma, biotech, devices)
Study start: Nov 2005
Primary completion: Feb 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 29 May 2006 (estimated)
Results: Posted 27 Jun 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This is a Phase IIIb open-label, multi-center, parallel dose, extension study conducted in approximately 40 centers across the United States.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
All rhIGF-1 Subjects	Experimental	Drug: rh IGF-1 (mecasermin)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.

Who may qualify

Ages: 4 to 15 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (3 listed)

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])

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
rh IGF-1 (mecasermin)Also: IncrelexPatients 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.	Drug	All rhIGF-1 Subjects

Primary outcome

Height Velocity During BID Dosing Period
Time frame: At Years 1, 2 and 3 in 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]).

4 secondary outcomes

Mean Change From Baseline in Height Standard Deviation (SD) Score During BID Dosing Period
Time frame: At baseline and Years 1, 2 and 3 in BID dosing period.
Mean Change From Baseline in Body Mass Index (BMI) SD Score During BID Dosing Period
Time frame: At baseline and Years 1, 2 and 3 in BID dosing period.
Mean Change From Baseline in Bone Age During BID Dosing Period
Time frame: At baseline and Years 1, 2 and 3 in BID dosing period.
Mean Change From Baseline in Predicted Adult Height During BID Dosing Period
Time frame: At baseline and Years 1, 2 and 3 in BID dosing period.

Results and safety

Results posted to the registry on 27 Jun 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All rhIGF-1 Subjects	114	78

Primary outcome: Height Velocity During BID Dosing Period

Time frame: At Years 1, 2 and 3 in BID dosing period.. Mean (Standard Deviation). Unit: cm/year

Measure	120 μg/kg rhIGF-1 BID (MITT Population) n = 55
Year 1	7.7 (1.5)
Year 2	6.1 (1.4)
Year 3	5.9 (1.1)

Population analysed: The modified Intent-To-Treat (MITT) population included subjects from the ITT population who were randomised to 120 μg/kg rhIGF-1 BID (either in MS301 or MS306). The subjects in the 80 μg/kg group were not analysed for efficacy due to the variations in their dose regimen and the duration of the regimen.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected for the overall study (including both the BID and QD dosing periods) from Day 1 until early termination of the study (up to 4 years, 3 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All rhIGF-1 Subjects	6 of 114 (5.3%)	107 of 114 (93.9%)	0 of 114

Limitations and caveats (from the sponsor): The study was terminated by the sponsor due to an unacceptably high incidence of hypoglycaemia observed in approximately 50% of the subjects receiving 200 μg/kg rhIGF-1 or greater QD.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sr Vice President, Clinical Development and Medical Affairs study director

Ipsen (formerly Tercica, Inc.)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rh IGF-1 (mecasermin) in people with Growth Disorders, run by Ipsen at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Height Velocity During BID Dosing Period (time frame: At Years 1, 2 and 3 in BID dosing period.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00330668.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2020.