IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01096784
First received: March 9, 2010
Last updated: May 13, 2016
Last verified: May 2016
  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 (ROP)
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 ]

Enrollment: 120
Study Start Date: June 2010
Study Completion Date: March 2016
Primary Completion Date: March 2016 (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
United States, Alabama
University of South Alabama Children's and Women's Hospital
Mobile, Alabama, United States, 36604-3391
United States, California
Univ of California Irvine Med Center
Irvine, California, United States, 92697
United States, Georgia
Georgia Regents Medical Center
Augusta, Georgia, United States, 30904
United States, Mississippi
Univ of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, North Carolina
Vidant Medical Center
Greenville, North Carolina, United States, 27834
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, West Virginia
West Virginia University Hospital
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
University of Wisconsin - Madison
Madision, Wisconsin, United States, 53715
Italy
D.A.I. Materno Infantile, S.O.D. Neonatologia e Terapia Intensiva Neonatale - Azienda Ospedaliero-Universitaria Careggi
Firenze, Italy
U.O.C Patologia e Terapia Intensiva Neonatale, Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico
Genova, Italy
University of Padua
Padua, Italy, 35128
Dipartimento per la Tutella della Salute della Donna e della Vita Nascente, del Bambino e dell'Adolescente-U.O.C. Neonatologia-Poli. Gemelli
Rome, Italy
Netherlands
VU medical Center
Amsterdam, Netherlands, 1081 HZ
Poland
Instytut Centrum Zdrowia Matki Polki
Lódz, Poland, 93-338
Ginekologiczno-Położniczy Szpital Kliniczny Uniwersytetu Medycznego w Poznani
Poznan, Poland, 60-535
Sweden
Skånes University Hospital Lund
Lund, Sweden
Karolinska Universtitetssjukhuset i Huddinge
Stockholm, Sweden
United Kingdom
Addenbrookes Hospital
Cambridge, United Kingdom, CB2 0QQ
St Peter's Hospital; Ashford & S
Chertsey, United Kingdom, KT16 OPZ
University Hospital
Coventry, United Kingdom, CV2 2DX
Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom
UCL EGA Institute for Women's Health
London, United Kingdom, WC1E 6AU
St. Mary's Hospital
Manchester, United Kingdom, M13 9WL
Norfolk and Norwich University
Norfolk, United Kingdom, NR4 7UY
Sponsors and Collaborators
Shire
Investigators
Study Director: Alexandra Mangili, MD, MPH Shire
Study Director: Adina Tocoian, MD, PhD Shire
  More Information

Publications:
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: May 13, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Sweden: Medical Products Agency

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

Additional relevant MeSH terms:
Premature Birth
Retinal Diseases
Retinopathy of Prematurity
Eye Diseases
Infant, Newborn, Diseases
Infant, Premature, Diseases
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications

ClinicalTrials.gov processed this record on May 24, 2016