IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity

NCT01096784 | Completed Phase 2 Results DMC

• 2 other identifiers: ROPP-2008-012007-007872-40
• Study Type: interventional
• Target: 121
• Locations: 6 countries
• Sites: 24

Brief Summary

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.

Conditions

Retinopathy of Prematurity (ROP)

Keywords

insulin-like growth factor; ROP; IGF-I; BPD; bronchopulmonary dysplasia; retinopathy of prematurity

Outcome Measures

Primary Outcomes (1)

• Severity of Retinopathy of Prematurity (ROP) as Compared to the Severity of ROP in an Untreated Control Population

  ROP was measured by central exams with fundus photography. Maximum severity of ROP stage across all retinal examinations included International Classification of Retinopathy of Prematurity, a 5 stage system, for the classification of ROP with 7 different outcomes of the ROP stage in each retinal examination: 0, 1, 2, 3, 3+, 4, and 5. This is an ordinal scale with higher numbers indicating a more severe outcome. The maximum severity of ROP across all time points was assessed from 31 PMA weeks up to 40 PMA Weeks +/- 4 days (end of study).

  End of study

Secondary Outcomes (13)

• Time to Discharge From Neonatal Intensive Care (TDNIC)

  Day 0 to 40 Weeks Post Menstrual Age (EOS)

• Number of Participants With Bronchopulmonary Dysplasia (BPD)

  At 36 Weeks Post Menstrual Age

• Rate of Change in Body Weight

  Day 0 to 40 Weeks Post Menstrual Age (EOS)

• Rate of Change in Length

  Day 0 to 40 Weeks Post Menstrual Age (EOS)

• Rate of Change in Head Circumference

  Day 0 to 40 Weeks Post Menstrual Age (EOS)

Study Arms (2)

rhIGF-I/rhIGFBP-3

ACTIVE COMPARATOR

Continuous IV Infusion

Drug: rhIGF-I/rhIGFBP-3

Control

NO INTERVENTION

The comparator group will receive no treatment with rhIGF-1/rhIGFBP-3

Interventions

rhIGF-I/rhIGFBP-3 DRUG

Continuous intravenous infusion

Also known as: Mecasermin Rinfabate

rhIGF-I/rhIGFBP-3

Eligibility Criteria

• Age: Up to 1 Day
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shire: lead

Study Sites (24)

University of South Alabama Children's and Women's Hospital

Mobile, Alabama, 36604-3391, United States

Location

Univ of California Irvine Med Center

Irvine, California, 92697, United States

Location

Georgia Regents Medical Center

Augusta, Georgia, 30904, United States

Location

Univ of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Vidant Medical Center

Greenville, North Carolina, 27834, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53715, United States

Location

D.A.I. Materno Infantile, S.O.D. Neonatologia e Terapia Intensiva Neonatale - Azienda Ospedaliero-Universitaria Careggi

Florence, Italy

Location

U.O.C Patologia e Terapia Intensiva Neonatale, Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e Cura a Carattere Scientifico

Genova, Italy

Location

University of Padua

Padua, 35128, Italy

Location

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

Location

VU medical Center

Amsterdam, 1081 HZ, Netherlands

Location

Instytut Centrum Zdrowia Matki Polki

Lódz, 93-338, Poland

Location

Ginekologiczno-Położniczy Szpital Kliniczny Uniwersytetu Medycznego w Poznani

Poznan, 60-535, Poland

Location

Skånes University Hospital Lund

Lund, Sweden

Location

Karolinska Universtitetssjukhuset i Huddinge

Stockholm, Sweden

Location

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

St Peter's Hospital; Ashford & S

Chertsey, KT16 OPZ, United Kingdom

Location

University Hospital

Coventry, CV2 2DX, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, United Kingdom

Location

UCL EGA Institute for Women's Health

London, WC1E 6AU, United Kingdom

Location

St. Mary's Hospital

Manchester, M13 9WL, United Kingdom

Location

Norfolk and Norwich University

Norwich, NR4 7UY, United Kingdom

Location

Related Publications (7)

• Lofqvist C, Niklasson A, Engstrom E, Friberg LE, Camacho-Hubner C, Ley D, Borg J, Smith LE, Hellstrom A. A pharmacokinetic and dosing study of intravenous insulin-like growth factor-I and IGF-binding protein-3 complex to preterm infants. Pediatr Res. 2009 May;65(5):574-9. doi: 10.1203/PDR.0b013e31819d9e8c.

  PMID: 19190540 BACKGROUND

• Ley D, Hansen-Pupp I, Niklasson A, Domellof M, Friberg LE, Borg J, Lofqvist C, Hellgren G, Smith LE, Hard AL, Hellstrom A. Longitudinal infusion of a complex of insulin-like growth factor-I and IGF-binding protein-3 in five preterm infants: pharmacokinetics and short-term safety. Pediatr Res. 2013 Jan;73(1):68-74. doi: 10.1038/pr.2012.146. Epub 2012 Oct 24.

  PMID: 23095978 RESULT

• Klevebro S, Hellgren G, Hansen-Pupp I, Wackernagel D, Hallberg B, Borg J, Pivodic A, Smith L, Ley D, Hellstrom A. Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants. Growth Horm IGF Res. 2020 Feb;50:1-8. doi: 10.1016/j.ghir.2019.11.001. Epub 2019 Nov 9.

  PMID: 31756675 DERIVED

• Ley D, Hallberg B, Hansen-Pupp I, Dani C, Ramenghi LA, Marlow N, Beardsall K, Bhatti F, Dunger D, Higginson JD, Mahaveer A, Mezu-Ndubuisi OJ, Reynolds P, Giannantonio C, van Weissenbruch M, Barton N, Tocoian A, Hamdani M, Jochim E, Mangili A, Chung JK, Turner MA, Smith LEH, Hellstrom A; study team. rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial. J Pediatr. 2019 Mar;206:56-65.e8. doi: 10.1016/j.jpeds.2018.10.033. Epub 2018 Nov 22.

  PMID: 30471715 DERIVED

• Hansen-Pupp I, Hellstrom A, Hamdani M, Tocoian A, Kreher NC, Ley D, Hallberg B. Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study. Growth Horm IGF Res. 2017 Oct;36:44-51. doi: 10.1016/j.ghir.2017.08.004. Epub 2017 Aug 31.

  PMID: 28934640 DERIVED

• Chung JK, Hallberg B, Hansen-Pupp I, Graham MA, Fetterly G, Sharma J, Tocoian A, Kreher NC, Barton N, Hellstrom A, Ley D. Development and verification of a pharmacokinetic model to optimize physiologic replacement of rhIGF-1/rhIGFBP-3 in preterm infants. Pediatr Res. 2017 Mar;81(3):504-510. doi: 10.1038/pr.2016.255. Epub 2016 Nov 21.

  PMID: 27870826 DERIVED

• Lundgren P, Stoltz Sjostrom E, Domellof M, Kallen K, Holmstrom G, Hard AL, Smith LE, Lofqvist C, Hellstrom A. WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants. PLoS One. 2013 Sep 12;8(9):e73256. doi: 10.1371/journal.pone.0073256. eCollection 2013.

  PMID: 24069180 DERIVED

MeSH Terms

Conditions

Retinopathy of Prematurity; Bronchopulmonary Dysplasia

Interventions

Insulin-Like Growth Factor I

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Somatomedins; Insulin-Like Peptides; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Blood Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2010
• First Posted: March 31, 2010
• Study Start: June 18, 2010
• Primary Completion: March 30, 2016
• Study Completion: March 30, 2016
• Last Updated: June 14, 2021
• Results First Posted: June 7, 2017

Record last verified: 2021-05

Locations

NL (1); US (8); IT (4); PL (2); SE (2); GB (7)