IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity

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

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.


Condition Intervention Phase
Retinopathy of Prematurity
Drug: rhIGF-I/rhIGFBP-3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 120
Study Start Date: June 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: rhIGF-I/rhIGFBP-3
Continuous IV Infusion
Drug: rhIGF-I/rhIGFBP-3
Continuous intravenous infusion
Other Name: Mecasermin Rinfabate
No Intervention: Control
The comparator group will receive no treatment with rhIGF-1/rhIGFBP-3

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 1 Day
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01096784

Locations
Italy
Careggi Hospital University Recruiting
Florence, Italy
Contact: Carlo Dani, MD    +39 055 7947792      
Principal Investigator: Carlo Dani, MD         
Gasilini Children's Hospital Not yet recruiting
Genova, Italy
Contact: Luca Ramenghi, MD         
Principal Investigator: Luca Ramenghi, MD         
Policlinico Gemelli Not yet recruiting
Rome, Italy
Contact: Constantino Romagnoli, MD         
Principal Investigator: Constantino Romagnoli, MD         
Netherlands
VU medical Center Not yet recruiting
Amsterdam, Netherlands
Contact: Mirjam Weissenbruch, MD         
Principal Investigator: Mirjam Weissenbruch, MD         
Poland
Ginekologiczno-Położniczy Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu Not yet recruiting
Poznań, Poland
Contact: Janusz Gadzinowski, MD         
Principal Investigator: Janusz Gadzinowski, MD         
Research Institute of Polish Mother Memorial Hospital Not yet recruiting
Rzgowska, Poland
Contact: Ewa Gulczyńska, MD         
Principal Investigator: Ewa Gulczyńska, MD         
Sweden
Lund University Hospital Not yet recruiting
Lund, Sweden
Contact: David Ley, MD, PhD         
Principal Investigator: David Ley, MD         
Karolinska University Hospital Not yet recruiting
Stockholm, Sweden
Contact: Boubou Hallberg, MD, PhD         
Principal Investigator: Boubou Hallberg, MD, PhD         
United Kingdom
Liverpool Women's Hospital Not yet recruiting
Liverpool, United Kingdom
Contact: Mark Turner, MD    00441517024084      
Principal Investigator: Mark Turner, MD         
UCL EGA Institute for Women's Health Not yet recruiting
London, United Kingdom
Contact: Neil Marlow, MD         
Principal Investigator: Neil Marlow, MD         
Sponsors and Collaborators
Shire
Investigators
Study Director: Nerissa Kreher, MD, MBA Shire
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01096784     History of Changes
Other Study ID Numbers: ROPP-2008-01, 2007-007872-40
Study First Received: March 9, 2010
Last Updated: August 11, 2014
Health Authority: Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire:
insulin-like growth factor
IGF-I
retinopathy of prematurity
ROP
bronchopulmonary dysplasia
BPD

Additional relevant MeSH terms:
Retinal Diseases
Retinopathy of Prematurity
Eye Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on September 18, 2014