To compare the severity of retinopathy of prematurity (ROP) among treated infants with an untreated control population, matched for GA at birth while confirming the dose of rhIGF 1/rhIGFBP-3 is safe and efficacious.
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
*To determine the effect of rhIGF-1/rhIGFBP-3 on the severity of ROP as
compared to the severity of ROP in an untreated control population.
*To evaluate the dose of rhIGF-1/rhIGFBP-3, administered by continuous IV
infusion, required to reach and maintain a physiological range of serum IGF-1
of 28 to 109 µg/L, defined as the in utero levels of IGF-1 for corresponding GA
in a normal population as described in Shire Reports 725-ROP-13-2103 and 725
ROP 13-2113.
*To determine serum concentrations of IGF-1 and associated pharmacokinetic
parameters after continuous IV infusion of rhIGF-1/rhIGFBP-3.
*To determine serum concentration of insulin-like growth factor binding protein
3 (IGFBP-3) and acid labile subunit (ALS) after continuous IV infusion of rhIGF
1/rhIGFBP-3.
Secondary outcome
To determine the effect of rhIGF-1/rhIGFBP-3 on other efficacy parameters and
determine the safety profile of rhIGF-1/rhIGFBP-3 when compared with standard
neonatal care in preterm infants.
Background summary
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, but it is likely there
are others. 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). Understanding which
factors are lost with preterm birth and evaluating their impact on the
development of ROP as well as for the growth and development of other organ
systems (brain, lungs, gut, and bones) is an important aim for this patient
population. Therefore, research in this field is of great importance for the
understanding of normal development of immature infants and for the prevention
of many complications of preterm birth.
Study objective
To compare the severity of retinopathy of prematurity (ROP) among treated
infants with an untreated control population, matched for GA at birth while
confirming the dose of rhIGF 1/rhIGFBP-3 is safe and efficacious.
Study design
A Phase 2, Randomized Controlled, Assessor-blind, Dose-confirming,
Pharmacokinetic, Safety and Efficacy, Multicenter Study
Intervention
Recombinant human insulin-like growth factor-1 (rhIGF-1)/recombinant human
insulin like growth factor binding protein-3 (rhIGFBP-3) administered by IV
infusion will be compared to standard of care.
The dose will be 250 µg/kg/24 hours via continuous IV infusion. Once initiated,
the IV infusion will be continued up to PMA 29 weeks + 6 days.
Study burden and risks
IGF-1 is an important growth factor needed for the body*s tissues and organs to
develop normally. Abnormally high levels of IGF-1 for a protracted period have
been associated with a risk of increased cell growth. The aim of this study is
to achieve normal levels of IGF-1 during the limited period of time when the
risk of developing ROP is greatest. Previous studies of children and adults
have shown that the blood sugar level can fall slightly when one is given
IGF-1. The blood sugar level will be monitored closely throughout the study. In
previous studies of premature infants, no safety risks have been discovered and
it has not been seen that mecasermin rinfabate has had any negative effects on
the blood sugar level. A drop in polyuria and one case of patent ductus
arteriosus that may be related to the study medicine have nevertheless been
found.
Even though the study medicine is a substitute for a protein that the body
itself produces, there is a small risk that antibodies are developed against
the product.
De Stadspoort 32
Eindhoven 5611 GZ
NL
De Stadspoort 32
Eindhoven 5611 GZ
NL
Listed location countries
Age
Inclusion criteria
Each subject must meet the following criteria to be enrolled in this study:;1- A signed written informed consent from the subject's parents/guardians prior to any study-related procedures that has been approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ;2- 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 who meet any of the following criteria will be excluded from the study:;1- Subjects born small for gestational age (SGA), ie, weight at birth <-2 SDS (Study Section A only);2- Detectable gross malformation;3- Known or suspected chromosomal abnormality, genetic disorder, or syndrome, according to the investigator*s opinion;4- Persistent plasma glucose level <2.5 mmol/L or >10 mmol/L at Study Day 0 to exclude severe congenital abnormalities of glucose metabolism;5- Anticipated need of administration of erythropoietin (rhEPO) during treatment with study drug;6- Maternal history of gestational diabetes or any diabetes requiring insulin while pregnant;7- Clinically significant neurological disease according to the investigator*s opinion (Stage 1 IVH allowed);8- 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;9- Monozygotic twins ;10- Subject participating or plans to participate in a clinical study of another investigational study drug
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | ClinicalTrial.gov ROPP-2008-01 |
| EudraCT | EUCTR2007-007872-40-NL |
| CCMO | NL48773.029.14 |