Insulin-Like Growth Factor I (IGF-I) in the Prevention of Complications of Preterm Birth

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Sahlgrenska University Hospital, Sweden
Lund University Hospital
Karolinska University Hospital
Information provided by (Responsible Party):
Premacure AB, a Member of the Shire Group of Companies
ClinicalTrials.gov Identifier:
NCT01096784
First received: March 9, 2010
Last updated: June 24, 2013
Last verified: June 2013

March 9, 2010
June 24, 2013
June 2010
December 2013   (final data collection date for primary outcome measure)
Severity of retinopathy of prematurity [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01096784 on ClinicalTrials.gov Archive Site
  • Incidence of mild and severe bronchopulmonary dysplasia [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
  • Body weight [ Time Frame: At birth, day 1, 2 and 3 and thereafter twice weekly up post menstrual age week 40 (appr.) ] [ Designated as safety issue: No ]
    Development of body weight in treated infants will be compared with untreated controls
  • Length [ Time Frame: Once weekly up to End of Study (at term age (post menstrual week 40)) ] [ Designated as safety issue: No ]
    Development of length in treated infants will be compared with untreated controls
  • Brain volume and head circumference [ Time Frame: Study days 1, 3, 7, 14, 21 and at PMA 6 weeks and at term age (post menstrual week 40) ] [ Designated as safety issue: No ]
    Development of brain volume and head circumference in treated infants will be compared with untreated controls
  • Number of days in neonatal intensive care [ Time Frame: At home discharge ] [ Designated as safety issue: No ]
    Total number of days in neonatal intensive care prior to home discharge for treated infants will be compared with untreated controls
  • Adverse events [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    Hematology, clinical chemistry, physical examinations and vital signs including heart rate, blood pressure, oxygen saturation and breath frequency will be monitored from birth throughout the study.
  • IGF-I levels [ Time Frame: From day of birth up to end of study ] [ Designated as safety issue: No ]
    IGF-I levels and associated pharmacokinetic parameters during and after continuous infusion of rhIGF-I/rhIGFBP-3 will be monitored from day of birth up to study end (postmenstrual week 40)
  • Blood glucose levels [ Time Frame: Throughout the treatment period ] [ Designated as safety issue: Yes ]
  • Long term follow up [ Time Frame: At 2.5 and 5.5 years of age ] [ Designated as safety issue: Yes ]
    All infants will be screened at 2.5 and 5.5 years of age with regard to visual development. Ocular fundus photographs for digital image analysis of the retinal vascular morphology will be taken at 2.5 and 5.5 years and at 5.5 years of age the children will have a clinical physical examination, including ultrasound of heart, kidney and spleen size, as well as a test of neuropsychologic functions (e.g. WISC) and test of pulmonary function. The pubertal development will be investigated by a pediatric endocrinologist at 10.5 years for the girls and at 12 years for the boys.
  • Incidence of mild and severe bronchopulmonary dysplasia [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
  • Body weight [ Time Frame: At birth, day 1, 2 and 3 and thereafter twice weekly up post menstrual age week 40 (appr.) ] [ Designated as safety issue: No ]
    Development of body weight in treated infants will be compared with untreated controls
  • Length [ Time Frame: Once weekly up to End of Study (at term age (post menstrual week 40)) ] [ Designated as safety issue: No ]
    Development of length in treated infants will be compared with untreated controls
  • Brain volume and head circumference [ Time Frame: Study days 1, 3, 7, 14, 21 and at PMA 6 weeks and at term age (post menstrual week 40) ] [ Designated as safety issue: No ]
    Development of brain volume and head circumference in treated infants will be compared with untreated controls
  • Number of days in neonatal intensive care [ Time Frame: At home discharge ] [ Designated as safety issue: No ]
    Total number of days in neonatal intensive care prior to home discharge for treated infants will be compared with untreated controls
  • Adverse events [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    Hematology, clinical chemistry, physical examinations and vital signs including heart rate, blood pressure, oxygen saturation and breath frequency will be monitored from birth throughout the study.
  • IGF-I levels [ Time Frame: From day of birth up to end of study ] [ Designated as safety issue: No ]
    IGF-I levels and associated pharmacokinetic parameters during and after continuous infusion of rhIGF-I/rhIGFBP-3 will be monitored from day of birth up to stusy end (postmenstrual week 40)
  • Blood glucose levels [ Time Frame: Throughout the treatment period ] [ Designated as safety issue: Yes ]
  • Long term follow up [ Time Frame: At 2.5 and 5.5 years of age ] [ Designated as safety issue: Yes ]
    All infants will be screened at 2.5 and 5.5 years of age with regard to visual development. Ocular fundus photographs for digital image analysis of the retinal vascular morphology will be taken at 2.5 and 5.5 years and at 5.5 years of age the children will have a clinical physical examination, including ultrasound of heart, kidney and spleen size, as well as a test of neuropsycologic functions (e.g. WISC) and test of pulmonary function. The pubertal development will be investigated by a pediatric endocrinologist at 10.5 years for the girls and at 12 years for the boys.
Not Provided
Not Provided
 
Insulin-Like Growth Factor I (IGF-I) in the Prevention of Complications of Preterm Birth
Determination of the rhIGF-I/rhIGFBP-3 Dose, Administered as a Continuous Infusion, Required to Establish and Maintain Longitudinal Serum IGF-I Levels Within Physiological Levels in Premature Infants, to Prevent Retinopathy of Prematurity.

This is a randomized multicenter trial on pharmacokinetics, safety and efficacy with administration of Insulin-Like Growth Factor I (IGF-I) in preterm infants to prevent complications of preterm birth.

Low Insulin-Like Growth Factor I (IGF-I) levels in premature infants between gestational ages of 23 and 40 weeks is a predictor of ROP. Restoration of IGF-I to normal in uteri levels may prevent ROP by allowing normal vessel growth and survival. An increase of serum IGF-I levels to approximately reach the level for corresponding gestational age (GA) of 20-60 μg/L, thus bringing levels to within physiological range, may prevent development of ROP.

In a phase-I pharmacokinetic study, the amount of recombinant human IGF-I (rhIGF-I), administered as a single infusion over three hours, required to produce Postmenstrual Age (PMA) levels of IGF-I within the normal intrauterine range for corresponding Gestational Age (GA)in premature infants was established. An algorithm was developed to predict the appropriate individual dose to reach levels of IGF-I corresponding to intrauterine levels when administering rhIGF-I as a continuous intravenous infusion.

In the present study, the dose of rhIGF-I needed, when administered as continuous infusion, to keep the PMA levels of IGF-I within the normal intrauterine range for corresponding GA from day after birth (study day 1) and up to and including maximally PMA age 31 weeks + 6 days (which is the same anticipated approach of a future preventive treatment), will be investigated. Moreover, the outcome on ROP development and other efficacy endpoints by increasing and maintaining the IGF-I levels to within intrauterine levels will be compared to a control group randomized to receive standard neonatal care without administration of study drug

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
  • Retinopathy of Prematurity
  • Bronchopulmonary Dysplasia
  • Body Weight
  • Body Length
  • Brain Volume
Drug: mecasermin rinfabate
Continuous intravenous infusion
Other Name: IGF-I
No Intervention: No IGF-I administration
Standard neonatology care without administration of IGF-I
Intervention: Drug: mecasermin rinfabate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
80
December 2013
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Signed informed consent from parents/guardians;
  • Subject must be between 26 weeks + 0 days and 27 weeks +6 days gestation (Section A) or between 23 weeks + 0 days and 27 weeks + 6 days gestation (Section B, C and Control Groups)

Exclusion Criteria:

  • Infants born small for gestational age (SGA), i.e. weight at birth <-2 SDS (Section A only);
  • Detectable gross malformation;
  • Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the investigator‟s opinion;
  • Persistent plasma glucose level <2.5 mmol/L or >10 mmol/L at study day 0 (day of birth);
  • Anticipated need of administration of erythropoietin (rhEPO) during treatment with study drug
  • Mother with diabetes requiring insulin;
  • Clinically significant neurological disease according to the investigator‟s opinion;
  • Any other condition or therapy that, in the investigator's opinion, may pose a risk to the subject or interfere with the subject‟s ability to be compliant with this protocol or interfere with interpretation of results.
Both
up to 1 Day
No
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT01096784
ROPP-2008-01, 2007-007872-40
Yes
Premacure AB, a Member of the Shire Group of Companies
Premacure AB, a Member of the Shire Group of Companies
  • Sahlgrenska University Hospital, Sweden
  • Lund University Hospital
  • Karolinska University Hospital
Principal Investigator: David Ley, MD, PhD Lund University Hospital, Sweden
Principal Investigator: Niklasson Aimon, MD, PhD Gothenburg University Hospital, Sweden
Principal Investigator: Boubou Hallberg, MD, PhD Karolinska University Hospital
Premacure AB, a Member of the Shire Group of Companies
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP