September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Determination of optimal dosing of rhIGF-1/rhIGFBP-3 to establish and maintain physiological intrauterine serum IGF-1 levels in preterm infants
Author Affiliations & Notes
  • Ann Hellstrom
    Sahlgrenska Academy, Gothenburg, Sweden
  • Boubou Hallberg
    Karolinska Institute and University Hospital, Stockholm, Sweden
  • Ingrid Hansen-Pupp
    Department of Pediatrics, Institute of Clinical Sciences Lund, Skane University Hospital and Lund University, Lund, Sweden
  • Jou-Ku Chung
    Shire, Lexington, Massachusetts, United States
  • Jyoti Sharma
    PKPD Bioscience Inc., Exton, Pennsylvania, United States
  • Gerald Fetterly
    Roswell Park Cancer Institute, Buffalo, New York, United States
  • Mary Ann Mascelli
    Shire, Lexington, Massachusetts, United States
  • Nerissa Kreher
    Shire, Lexington, Massachusetts, United States
  • Norman Barton
    Shire, Lexington, Massachusetts, United States
  • David Ley
    Department of Pediatrics, Institute of Clinical Sciences Lund, Skane University Hospital and Lund University, Lund, Sweden
  • Footnotes
    Commercial Relationships   Ann Hellstrom, Premalux AB (I), Shire (C); Boubou Hallberg, Premacure AB (C); Ingrid Hansen-Pupp, Premalux AB (I), Shire (C); Jou-Ku Chung, Shire (E); Jyoti Sharma, PKPD Bioscience Inc. (E); Gerald Fetterly, PKPD Bioscience Inc. (E), Shire (C); Mary Ann Mascelli, Shire (E); Nerissa Kreher, Shire (E); Norman Barton, Shire (E); David Ley, Premalux AB (I)
  • Footnotes
    Support  This study was funded by Premacure AB, a member of the Shire group of companies. The authors thank Valerie Boissel PhD, of Excel Scientific Solutions, who provided medical writing assistance funded by Shire.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6278. doi:
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      Ann Hellstrom, Boubou Hallberg, Ingrid Hansen-Pupp, Jou-Ku Chung, Jyoti Sharma, Gerald Fetterly, Mary Ann Mascelli, Nerissa Kreher, Norman Barton, David Ley; Determination of optimal dosing of rhIGF-1/rhIGFBP-3 to establish and maintain physiological intrauterine serum IGF-1 levels in preterm infants. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6278.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : rhIGF-1/rhIGFBP-3 is being investigated for the prevention of retinopathy of prematurity in preterm infants. A population pharmacokinetic (PK) model was developed using data from phase 1 and 2 (Sections A-C) studies of rhIGF-1/rhIGFBP-3 in preterm infants in order to predict optimal dosing to establish and maintain serum IGF-1 within physiological intrauterine levels. Section D of the phase 2 study, evaluating dosing/efficacy of rhIGF-1/rhIGFBP-3, was initiated using the predicted dose. We report serum IGF-1 levels for the first 10 infants treated in Section D.

Methods : The phase 2 Section D study is ongoing in infants with gestational age (GA; wk+d) 23+0 to 27+6 at birth, randomized to rhIGF-1/rhIGFBP-3 or standard of care; target enrollment is 120 infants. rhIGF-1/rhIGFBP-3 is administered at 250 µg/kg/d by continuous intravenous (IV) infusion from birth up to a postmenstrual age of 29 wk+6 d. A review of serum IGF-1 data was conducted once 10 treated infants completed the dosing phase of the study to assess suitability of the dose regimen to reach and maintain serum IGF-1 target levels of 28–109 μg/L (physiological intrauterine levels for GA 23–28 wk based on published literature).

Results : Serum IGF-1 data were reviewed for 10 treated (50.0% male) and 9 control infants (66.7% male). At birth, GA (wk+d) ranged from 24+4–27+5 for treated and 23+3–27+6 for control infants; birth weight ranged from 0.5–1.1 kg and 0.6–1.2 kg, respectively. Duration of therapy in treated infants ranged from 1–34 days. At baseline, mean (SD) serum IGF-1 was 19.2 (8.0) μg/L for treated and 15.4 (4.7) μg/L for control infants. Mean (SD) serum IGF-1 levels increased to 45.9 (19.6) μg/L at 12h in treated infants, and remained within target levels for all subsequent timepoints. In controls, mean serum IGF-1 remained below target levels for all timepoints. Overall, 88.8% of serum IGF-1 measurements were within target levels for treated infants (11.1% for controls).

Conclusions : Using the selected dose of rhIGF-1/rhIGFBP-3 (250 µg/kg/d by continuous IV infusion), serum IGF-1 levels were within targeted, physiological intrauterine levels for the majority of measurements in treated infants. This analysis validates the population PK model and confirms the appropriateness of the designed dosing regimen for Section D.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

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