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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a
Ingrid Hansen-Pupp1, Ann Hellström2, Mohamed Hamdani3
1Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lasarettsgatan 40, SE-221 85 Lund, Sweden.
Insights
Continuous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) is feasible for extremely preterm infants. This treatment effectively increased IGF-1 levels without significant safety concerns.
Area of Science:
- Neonatal Medicine
- Endocrinology
- Pharmacology
Background:
- Retinopathy of prematurity (ROP) and other complications affect extremely preterm infants (<28 weeks' gestational age).
- Growth factors like insulin-like growth factor-1 (IGF-1) play crucial roles in fetal development.
Purpose of the Study:
- To assess the feasibility of continuous longitudinal intravenous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants.
- To evaluate the safety and efficacy of rhIGF-1/rhIGFBP-3 in achieving target serum IGF-1 levels.
Main Methods:
- Phase II randomized controlled trial (Sections B and C) involving 19 extremely preterm infants.
- Infants received either rhIGF-1/rhIGFBP-3 or standard neonatal care.
- Dosing was individualized to maintain serum IGF-1 within physiological intrauterine levels.
Main Results:
- rhIGF-1/rhIGFBP-3 infusion increased mean serum IGF-1 levels compared to controls (23 μg/L vs. 14 μg/L).
- 66.3% of IGF-1 measurements in treated infants were within the target range (20-60 μg/L).
- Adverse events were similar between groups, with no treatment-related safety signals or increased infection rates.
Conclusions:
- Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 is feasible and well-tolerated in extremely preterm infants.
- The treatment effectively increased serum IGF-1 concentrations.
- Further optimization of dosing regimens is needed, but results support the potential of this therapy.
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 (<28weeks' 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 23μg/L among treated infants compared with 14μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20-60μg/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).