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IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01096784
First received: March 9, 2010
Last updated: November 11, 2014
Last verified: November 2014

March 9, 2010
November 11, 2014
June 2010
July 2015   (final data collection date for primary outcome measure)
Severity of Retinopathy of Prematurity (ROP) as compared to the severity of ROP in an untreated control population. [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
Severity of retinopathy of prematurity [ Time Frame: At term age (post menstrual week 40) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01096784 on ClinicalTrials.gov Archive Site
  • Time to discharge from neonatal intensive care (TDNIC) [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
  • Development of bronchopulmonary dysplasia, by severity [ Time Frame: 36 Weeks Post Menstrual Age ] [ Designated as safety issue: No ]
  • Body weight [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
    Body weight of treated infants will be compared with untreated controls
  • Length [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
    Length of treated infants will be compared with untreated controls
  • Brain development as assessed by changes in head circumference [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
    Head circumference of treated infants will be compared with untreated controls
  • Brain development as assessed by changes in brain volume [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
    Brain volume of treated infants will be compared with untreated controls
  • Development of intraventricular hemorrhage (IVH) [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
  • Area under curve for maximum severity of ROP stage (AUC for ROP) [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
    Integration of the maximum severity of ROP stage and the duration of the time interval with respect to each retinal examination.
  • Development of maximum severity of ROP stage ≥3 at any time during the study [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: No ]
  • Adverse Event [ Time Frame: Day 0 to 40 Weeks Post Menstrual Age (EOS) ] [ Designated as safety issue: Yes ]
    Clinical laboratory parameters (blood glucose, hematology, clinical chemistry, blood gas measurements), anti-IGF-1/IGFBP-3 antibodies, physical examination, vital signs, concomitant medications/procedures, and echocardiogram
  • Serum concentrations of IGF-1 after IV infusion of rhIGF-1/rhIGFBP-3 [ Time Frame: Day 0 to 29 Weeks + 6 days Post Menstrual Age ] [ Designated as safety issue: No ]
  • Serum concentrations of IGFBP-3 after IV infusion of rhIGF-1/rhIGFBP-3 [ Time Frame: Day 0 to 29 Weeks + 6 days Post Menstrual Age ] [ Designated as safety issue: No ]
  • Serum concentrations of ALS after IV infusion of rhIGF-1/rhIGFBP-3 [ Time Frame: Day 0 to 29 Weeks+6 days Post Menstrual Age ] [ Designated as safety issue: No ]
  • 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
 
IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity
Determination of the rhIGF-1/rhIGFBP-3 Dose, Administered as a Continuous Infusion, Required to Establish and Maintain Longitudinal Serum IGF-1 Levels Within Physiological Levels in Premature Infants, to Prevent Retinopathy of Prematurity A Phase 2, Randomized Controlled, Assessor-blind, Dose Confirming, Pharmacokinetic, Safety and Efficacy, Multicenter Study

To compare the severity of retinopathy of prematurity (ROP) among treated infants with an untreated control population, matched for gestational age at birth while confirming the dose of rhIGF-1/rhIGFBP-3 is safe and efficacious.

When preterm infants are deprived of their natural intrauterine environment they lose access to important factors, normally found in utero, such as proteins, growth factors, and cytokines. It has been demonstrated that insulin-like growth factor-1 (IGF-1) is one such factor. In utero these biological factors are introduced to the fetus via placental absorption or ingestion from amniotic fluid. Deprivation of such factors is likely to cause inhibition or improper stimulation of important pathways, which in the case of the eye may cause abnormal retinal vascular growth, the hallmark of retinopathy of prematurity (ROP).

Retinopathy of prematurity is the major cause of blindness in children in the developed and developing world, despite the availability of current treatment of late-stage ROP. As developing countries provide more neonatal and maternal intensive care, which increases the survival of preterm born infants, the incidence of ROP is increasing.

This phase 2 study was originally designed in 3 sections, Sections A, B, and C which are now complete. The protocol was amended and patients enrolled from this point forward will be enrolled into Section D.

In Study Section D, a total of 120 subjects (GA of 23 weeks + 0 days to 27 weeks + 6 days) will be randomly assigned with 1:1 allocation ratio to either treatment with rhIGF-1/rhIGFBP-3 or to receive standard neonatal care (Control Group) to obtain at least 80 evaluable subjects. Duration of infusion will last at longest from Study Day 0 (day of birth) up to and including PMA 29 weeks + 6 days, when the subject's endogenous production of IGF-1 is considered sufficient to maintain physiologic serum IGF-1 levels. After discontinuation of study drug infusion, each subject will be followed to PMA 40 weeks ± 4 days.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Retinopathy of Prematurity
Drug: rhIGF-I/rhIGFBP-3
Continuous intravenous infusion
Other Name: Mecasermin Rinfabate
  • Active Comparator: rhIGF-I/rhIGFBP-3
    Continuous IV Infusion
    Intervention: Drug: rhIGF-I/rhIGFBP-3
  • No Intervention: Control
    The comparator group will receive no treatment with rhIGF-1/rhIGFBP-3

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Signed informed consent from parents/guardians;
  • Subject must be between GA of 26 weeks + 0 days and 27 weeks + 6 days (Study Section A) or between GA of 23 weeks + 0 days and 27 weeks + 6 days (Study Sections B, C, and D), inclusive

Exclusion Criteria:

  • Subjects born small for gestational age (SGA), ie, body weight at birth <-2 standard deviation score (SDS) (Study Section A only)
  • Detectable gross malformation
  • Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the Investigator's opinion
  • Persistent blood glucose level <2.5 mmol/L or >10 mmol/L at Study Day 0 (day of birth) to exclude severe congenital abnormalities of glucose metabolism
  • Anticipated need of administration of erythropoietin (rhEPO) during treatment with study drug.
  • Any maternal diabetes requiring insulin during the pregnancy
  • Clinically significant neurological disease according to the Investigator's opinion(Stage 1 IVH allowed)
  • 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
  • Monozygotic twins
  • Subject participating or plans to participate in a clinical study of another investigational study drug
Both
up to 1 Day
No
Italy,   Netherlands,   Sweden,   United Kingdom
 
NCT01096784
ROPP-2008-01, 2007-007872-40
Yes
Shire
Shire
Not Provided
Study Director: Nerissa Kreher, MD, MBA Shire
Shire
November 2014

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