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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants : Evaluation of feasibility in a phase II study

Hansen-Pupp, Ingrid LU ; Hellström, Ann LU ; Hamdani, Mohamed; Tocoian, Adina; Kreher, Nerissa C.; Ley, David LU and Hallberg, Boubou (2017) In Growth Hormone and IGF Research 36. p.44-51
Abstract

Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (< 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was... (More)

Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (< 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. Results Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6) μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1) days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23 μg/L among treated infants compared with 14 μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20–60 μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). Conclusion Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784).

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Complications of prematurity, Continuous infusion, IGF-1, Preterm infants, Randomized controlled trial, Retinopathy of prematurity, rhIGF-1/rhIGFBP-3
in
Growth Hormone and IGF Research
volume
36
pages
44 - 51
publisher
Elsevier
external identifiers
  • scopus:85029548269
  • wos:000415777200007
ISSN
1096-6374
DOI
10.1016/j.ghir.2017.08.004
language
English
LU publication?
yes
id
a6fa6441-29da-4492-906d-659d322572cb
date added to LUP
2017-10-06 11:26:05
date last changed
2018-01-16 13:21:31
@article{a6fa6441-29da-4492-906d-659d322572cb,
  abstract     = {<p>Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (&lt; 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. Results Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6) μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1) days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23 μg/L among treated infants compared with 14 μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20–60 μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). Conclusion Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784).</p>},
  author       = {Hansen-Pupp, Ingrid and Hellström, Ann and Hamdani, Mohamed and Tocoian, Adina and Kreher, Nerissa C. and Ley, David and Hallberg, Boubou},
  issn         = {1096-6374},
  keyword      = {Complications of prematurity,Continuous infusion,IGF-1,Preterm infants,Randomized controlled trial,Retinopathy of prematurity,rhIGF-1/rhIGFBP-3},
  language     = {eng},
  month        = {10},
  pages        = {44--51},
  publisher    = {Elsevier},
  series       = {Growth Hormone and IGF Research},
  title        = {Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants : Evaluation of feasibility in a phase II study},
  url          = {http://dx.doi.org/10.1016/j.ghir.2017.08.004},
  volume       = {36},
  year         = {2017},
}