Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study. (October 2017)

• Record Type: Journal Article
• Authors: Hansen-Pupp, Ingrid; Hellström, Ann; Hamdani, Mohamed; Tocoian, Adina; Kreher, Nerissa C.; Ley, David; Hallberg, Boubou
• Is Part Of: Growth hormone & IGF research. Volume 36(2017)
• Page Start: 44
• Page End: 51
• Publication Date: 2017-10
• Subjects: AE adverse event -- BPD bronchopulmonary dysplasia -- GA gestational age -- IGF-1 insulin-like growth factor-1 -- IGFBP-3 insulin-like growth factor binding protein-3 -- IV intravenous -- IVH intraventricular hemorrhage -- MedDRA Medical Dictionary for Regulatory Activities -- PK pharmacokinetic -- PMA postmenstrual age -- rh recombinant human -- rhIGF-1/rhIGFBP-3 recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 -- ROP retinopathy of prematurity -- SAE serious adverse event -- SD standard deviation -- TEAE treatment-emergent adverse event; IGF-1 -- Continuous infusion -- Complications of prematurity -- Preterm infants -- Randomized controlled trial -- Retinopathy of prematurity -- rhIGF-1/rhIGFBP-3; Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2017.08.004
• Languages: English
• ISSNs: 1096-6374

Abstract

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 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 atClinicalTrials.gov (NCT01096784 ). Highlights: rhIGF-1/rhIGFBP-3 is being studied for prevention of complications of prematurity. Continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants is evaluated. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals.