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

NCT00330668 | Terminated Phase 3 Results DMC

• 2 other identifiers: MS3062019-000844-81
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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.

Conditions

Growth Disorders

Keywords

Insulin-like Growth Factor Deficiency; IGF-1; Short Stature

Outcome Measures

Primary Outcomes (1)

• 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 \[2-3 years\]).

  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

  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

  At baseline and Years 1, 2 and 3 in BID dosing period.

• Mean Change From Baseline in Bone Age During BID Dosing Period

  At baseline and Years 1, 2 and 3 in BID dosing period.

• Mean Change From Baseline in Predicted Adult Height During BID Dosing Period

  At baseline and Years 1, 2 and 3 in BID dosing period.

Study Arms (1)

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.

Drug: rh IGF-1 (mecasermin)

Interventions

rh IGF-1 (mecasermin) DRUG

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.

Also known as: Increlex

All rhIGF-1 Subjects

Eligibility Criteria

• Age: 4 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 \[NCT00125164\])

You may not qualify if:

• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (1)

Ipsen

Paris, France

Location

MeSH Terms

Conditions

Growth Disorders; Dwarfism

Interventions

mecasermin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Ipsen Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

See email

Study Officials

• Sr Vice President, Clinical Development and Medical Affairs

  Ipsen (formerly Tercica, Inc.)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: November 1, 2005
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: August 14, 2020
• Results First Posted: June 27, 2011

Record last verified: 2020-08

Locations

FR (1)