rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial

Abstract

Objective To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. Study design This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 23 0/7 weeks to 27 6/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 μ g/kg/24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 29 6/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 40 4/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28–109 μ g/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. Results Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3–4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. Conclusions rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3–4 intraventricular hemorrhage. Trial registration ClinicalTrials.gov : NCT01096784 .

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review

“…The effect of a recombinant human supplement and in higher dosages needs to be investigated in future trials. Intravenous supplementation of rhIGF-1 together with its binding protein resulted in a recent phase 2 trial in a reduction of BPD rates [ 56 ]. Currently, a phase 3 study is enrolling patients.…”

The Relation Between Serum Levels of Insulin-like Growth Factor-1 and Bronchopulmonary Dysplasia

“…Anjiyogenezis hem ROP gelişimi, hem de BPD gelişimi ile olduğundan, ayrıca deneysel çalışmalarda IGF-1 tedavisi uygulanmasının intraventriküler kanama üzerine olumlu etkileri gösterildiğinden ROP, BPD ve nörogelişimsel etkileri açısından postnatal IGF-1 tedavilerinin Faz 1 çalışmaları tamamlanmış ve çok merkezli randomize Faz 2 çalışmaları sürmektedir. Sürekli IGF-1 infüzyonunun ağır BPD'yi azalttığı gösterilmiştir (26,27) .…”

Current evidence and outcomes for retinopathy of prematurity prevention: insight into novel maternal and placental contributions

“…In a small pilot trial, preterm infants were treated with a continuous infusion of recombinant human IGF-1 (rhIGF-1) and its receptor IGF binding protein-3 (rhIGFBP-3) which demonstrated increased IGF-1 and IGFBP-3 serum concentrations without safety concerns [72]. However, recently published Phase II clinical trials reported no reduction in ROP occurrence or severity after supplemental human rhIFG-I/rhIGFBP-3 administration [73]. As noted by the authors, the IGF-1 treatment effect may be unavoidably masked by high oxygen supplementation; however, as supplemental oxygen continues to be an important part of clinical care, IGF-1 supplementation does not appear to provide a viable monotherapy for ROP prevention.…”