Insulin-like Growth Factor-1 DeficiencyPhase 2NCT00572156

rhGH and rhIGF-1 Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency

A Phase 2 study testing NutropinAq® (Somatropin [rDNA origin]) and Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin]) in people with Insulin-like Growth Factor-1 Deficiency, run by Ipsen at 1 site in United States.

Terminated

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

Official record

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Trial summary

IGF-1 (insulin-like growth factor-1) is a hormone that is normally produced in the body in response to another hormone called growth hormone. Growth Hormone is produced by a small gland at the base of the brain (the pituitary). Read more about this study

Who is it for?: Ages 5 years and older
Conditions the study is for: Insulin-like Growth Factor-1 Deficiency
What is being tested?: NutropinAq® (Somatropin [rDNA origin]) and Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 106 participants
Where: 1 siteUnited States
Study dates: Dec 2007to Mar 2012
Phase: Phase 2
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 5 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Parents or legally authorized representatives must give signed informed consent before any trial-related activities
IGF-1 SDS of ≤ -1 for age and gender
Short stature, as defined by a height SDS of ≤ -2 for age and gender
Chronological age ≥ 5 years
Bone age ≤ 11 years in boys and ≤ 9 years in girls
GH sufficiency, defined as a maximal stimulated GH response of greater than or equal to 10 ng/mL at Visit 2 (note: upon approval of the Medical Monitor, the result of a prior GH stimulation test may satisfy this requirement).
Prepubertal status
Adequate nutrition as evidenced by a body mass index (BMI) greater than or equal to the 5th percentile for age and gender

Who cannot join

Severe Primary IGFD (defined as height and IGF-1 SDS ≤ 3, and stimulated GH response greater than or equal to 10 ng/mL)
Prior or current use of medications with the potential to alter growth patterns including GH, IGF-1, IGFBP-3, gonadotrophin agonists (e.g., Lupron), aromatase inhibitors, androgens and estrogens
Known or suspected allergy to rhGH, rhIGF-1 or a constituent of their formulations
Current use of medications for attention deficit disorder
A chronic health condition that requires anti-inflammatory steroids or daily medication unless approved by the Medical Monitor

Trial locations and contacts

1 site in 1 country.

United States1 site

Ipsen
Brisbane, California, 94005

Other trials in United States

About this study

Official title: Recombinant Human Growth Hormone (rhGH) and Recombinant Human Insulin-like Growth Factor-1 rhIGF-1) Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency: A Six-year, Randomized, Multi-center, Open-label, Parallel-group, Active Treatment Controlled, Dose Selection Trial

Children with IGF Deficiency are short and have an imbalance in the levels of growth hormone and IGF-1 that their body produces. Their growth hormone levels are normal or even high, but IGF-1 levels do not increase normally in response to growth hormone. As a result, they have a type of growth hormone insensitivity and an inability to grow normally.

This study is a test to see whether daily dosing with a combination of rhIGF-1 and rhGH will help children with IGFD grow taller more quickly than children treated with rhGH alone. The study medications, rhIGF-1 and rhGH, are approved by the US Food and Drug Administration (FDA) for use in some growth disorders in children, but the combination of rhIGF-1 and rhGH in children with IGF-1 deficiency (IGFD) is investigational.

Conditions: Insulin-like Growth Factor-1 Deficiency
Being tested: NutropinAq® (Somatropin [rDNA origin]), Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
Keywords: IGF-1 Deficiency, growth, ISS, Constitutional growth delay, Primary IGFD, Primary IGF Deficiency
Medical subject headings: Insulin-Like Growth Factor I Deficiency, Puberty, Delayed

What participants receive

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

NutropinAq® (Somatropin [rDNA origin])Drug
Also called GH
rhGH (Somatropin) 45µg/kg once daily injection
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Drug
Also called Increlex, rhIGF-1, GH
rhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Drug
Also called Increlex, rhIGF-1, GH
rhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Drug
Also called Increlex, rhIGF-1, GH
rhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections

Study groups in NCT00572156
Study group	Role	What they receive
1. rhGH Alone	Active comparator	Not described Receives: Drug: NutropinAq® (Somatropin [rDNA origin])
2. Combination Dose	Experimental	Not described Receives: Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
3. Combination Dose	Experimental	Not described Receives: Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
4. Combination Dose	Experimental	Not described Receives: Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

What is being measured

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

Height Velocity
Measured: First year of treatment

Secondary outcomes (12)

Height Velocity
Measured: Second, third and fourth year
Cumulative Change in Height Standard Deviation Score (SDS)
Height was measured standing and without shoes, and recorded as the mean of three measurements (the subject being repositioned each time) by the same observer using a Harpenden or other wall-mounted stadiometer which was to be calibrated prior to measurement of each subject and a calibration log kept.
The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Measured: First, second, third and fourth year
Predicted Adult Height (PAH)
Predicted Adult Height calculated by method, Roche-Wainer-Thissen (RWT) and mid-parental target height SDS.
The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Measured: At baseline (Day 1), year 1,2,3 and 4
Total Change From Baseline (Day 1) in BMI SDS
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2).
The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Measured: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)
Skeletal Maturation
Assessed by bone age. Bone age was determined by the radiograph.
The SDS was calculated as: SDS=[(value /M)^L - 1] / LS; using power (L), Mean (M) and coefficient of variation (S). The reference values were dependent on gender in addition to age and were selected at the age the closest below subject's age. SDS scores were calculated using L, M and S as defined in the National Center for Health Statistics 2000 data as provided by the Center for Disease Control (Kuczmarski, Ogden et al. 2002)
Measured: At baseline(day 1), year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)
Measured: At Baseline (Day 1), Year 1,2,3 and 4
Summary of Adverse Events With Number of Occurrences
A Data Monitoring Committee (DMC) was established to monitor subject safety
Measured: Approximately up to 4 years.

Timeline

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

Dec 2007Mar 2012

First posted12 Dec 2007 (estimated)
Study startDec 2007
Primary completionApr 2010
Study completionMar 2012

Why it stopped: The study was prematurely terminated due to strategic reasons.

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 Insulin-like Growth Factor-1 DeficiencyStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 106 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00572156
Sponsor's protocol ID: MS316
Other IDs: 2019-000843-29, 2019
Status last verified: Mar 2023
First submitted: 10 Dec 2007
Last updated: 30 Mar 2023
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?

See locations

RecruitingObservational study
Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).
IGF1 Deficiency

All Insulin-like Growth Factor-1 Deficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Recombinant Human Growth Hormone (rhGH) and Recombinant Human Insulin-like Growth Factor-1 rhIGF-1) Combination Therapy in Children With Short Stature Associated With IGF-1 Deficiency: A Six-year, Randomized, Multi-center, Open-label, Parallel-group, Active Treatment Controlled, Dose Selection Trial
ClinicalTrials.gov ID: NCT00572156
Acronym / sponsor ID: MS316
Conditions: Insulin-like Growth Factor-1 Deficiency
Keywords: IGF-1 Deficiency, growth, ISS, Constitutional growth delay, Primary IGFD, Primary IGF Deficiency
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was prematurely terminated due to strategic reasons.
Enrolment: 106 participants (actual)
Lead sponsor: IpsenIndustry (pharma, biotech, devices)
Study start: Dec 2007
Primary completion: Apr 2010 (actual)
Study completion: Mar 2012 (actual)
First posted: 12 Dec 2007 (estimated)
Results: Posted 15 Dec 2015

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
1. rhGH Alone	Active comparator	Drug: NutropinAq® (Somatropin [rDNA origin])
2. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
3. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])
4. Combination Dose	Experimental	Drug: Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])

Who may qualify

Ages: 5 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

Parents or legally authorized representatives must give signed informed consent before any trial-related activities
IGF-1 SDS of ≤ -1 for age and gender
Short stature, as defined by a height SDS of ≤ -2 for age and gender
Chronological age ≥ 5 years
Bone age ≤ 11 years in boys and ≤ 9 years in girls

Key exclusion criteria (5 listed)

Severe Primary IGFD (defined as height and IGF-1 SDS ≤ 3, and stimulated GH response greater than or equal to 10 ng/mL)
Prior or current use of medications with the potential to alter growth patterns including GH, IGF-1, IGFBP-3, gonadotrophin agonists (e.g., Lupron), aromatase inhibitors, androgens and estrogens
Known or suspected allergy to rhGH, rhIGF-1 or a constituent of their formulations
Current use of medications for attention deficit disorder
A chronic health condition that requires anti-inflammatory steroids or daily medication unless approved by the Medical Monitor

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
NutropinAq® (Somatropin [rDNA origin])Also: GHrhGH (Somatropin) 45µg/kg once daily injection	Drug	1. rhGH Alone
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Also: Increlex, rhIGF-1, GHrhGH 45µg/kg and rhIGF-1 150µg/kg once daily injection	Drug	4. Combination Dose
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Also: Increlex, rhIGF-1, GHrhGH (Somatropin) 45µg/kg and rhIGF-1 (Mecasermin) 50µg/kg once daily injections	Drug	2. Combination Dose
Increlex® (Mecasermin [rDNA origin] injection) + NutropinAq® (Somatropin [rDNA origin])Also: Increlex, rhIGF-1, GHrhGH 45µg/kg and rhIGF-1 100µg/kg once daily injections	Drug	3. Combination Dose

Primary outcome

Height Velocity
Time frame: First year of treatment

12 secondary outcomes

Height Velocity
Time frame: Second, third and fourth year
Cumulative Change in Height Standard Deviation Score (SDS)
Time frame: First, second, third and fourth year
Predicted Adult Height (PAH)
Time frame: At baseline (Day 1), year 1,2,3 and 4
Total Change From Baseline (Day 1) in BMI SDS
Time frame: At year 1,2,3,4 and end of study (visit 23) versus baseline (day 1)
Skeletal Maturation
Time frame: At baseline(day 1), year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone (GH)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor-1 (IGF-1)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Insulin-Like Growth Factor Binding Protein-3 (IGFPB-3)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Acid-Labile Subunit (ALS)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Changes From Baseline (Day 1) in Serum Concentrations of Growth Hormone Binding Protein (GHBP)
Time frame: At Baseline (Day 1), Year 1,2,3 and 4
Summary of Adverse Events With Number of Occurrences
Time frame: Approximately up to 4 years.

Results and safety

Results posted to the registry on 15 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
45 rhGH Alone	26	0
45 rhGH + 50 rhIGF-1	27	1
45 rhGH + 100 rhIGF-1	27	0
45 rhGH + 150 rhIGF-1	26	1

Primary outcome: Height Velocity

Time frame: First year of treatment. Mean (Standard Deviation). Unit: cm/y

Measure	rhGH Alone n = 25	45 rhGH + 50 rhIGF-1 n = 27	45 rhGH + 100 rhIGF-1 n = 27	45 rhGH + 150 rhIGF-1 n = 26
Value	9.3 (1.7)	10.1 (1.3)	9.7 (2.5)	11.2 (2.1)

Population analysed: Modified Intent-To-Treat (MITT): MITT population comprised all subjects who were randomized and had at least one post-baseline height measurement. \[n= 25,27,27,26\]

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Approximate up to 4 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
1. rhGH Alone	1 of 26 (3.8%)	26 of 26 (100%)	Not reported
2. 45 rhGH + 50 rhIGF-1	1 of 27 (3.7%)	27 of 27 (100%)	Not reported
3. 45 rhGH + 100 rhIGF-1	2 of 27 (7.4%)	27 of 27 (100%)	Not reported
4. 45 rhGH + 150 rhIGF-1	1 of 26 (3.8%)	26 of 26 (100%)	Not reported

Limitations and caveats (from the sponsor): The study was prematurely terminated once the last subject had completed three years of treatment (compared to the six years planned in protocol Amendment) for strategic reasons.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Insulin-like Growth Factor-1 Deficiency

RecruitingObservational study
Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).
IGF1 Deficiency

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.

Ipsen Medical Director 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?

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 8 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 30 Mar 2023. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 15 Dec 2015). 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 (time frame: First year of treatment). 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 NCT00572156.

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 30 Mar 2023.

Trial summary

Key requirements

Who may be able to join

Who cannot join

Trial locations and contacts

About this study

What participants receive

What is being measured

Timeline

Resources

More details

Study at a glance

Clinical summary

Study design

Who may qualify

Key inclusion criteria (8 listed)

Key exclusion criteria (5 listed)

Interventions

Primary outcome

Results and safety

Participant flow

Primary outcome: Height Velocity

Adverse events

Research links

Related trials for Insulin-like Growth Factor-1 Deficiency

Global Patient Registry to Monitor Long-term Safety and Effectiveness of Increlex® in Children and Adolescents With Severe Primary Insulin-like Growth Factor-1 Deficiency (SPIGFD).

Referral and contact

Questions about this trial

Participant flow

Primary outcome: Height Velocity

Adverse events