David Ley , MD, PhD 1 , Boubou Hallberg , MD, PhD 2 , Ingrid Hansen-Pupp , MD, PhD 1 , Carlo Dani , MD 3 , Luca A. Ramenghi , MD, PhD 4 , Neil Marlow , DM, FMedSci 5 , Kathryn Beardsall , MD 6 , Faizah Bhatti , MD 7 , David Dunger , MD 6 , Jason D. Higginson , MD 8 , Ajit Mahaveer , MRCPCH 9 , Olachi J. Mezu-Ndubuisi , MD, OD 10 , Peter Reynolds , MB.BS, PhD 11 , Carmen Giannantonio , MD, PhD 12 , Mirjam van Weissenbruch , MD, PhD 13 , Norman Barton , MD, PhD 14 , Adina Tocoian , MD, PhD 15 , Mohamed Hamdani , MS 14 , Emily Jochim , MBA 14 , Alexandra Mangili , MD, MPH 15 , Jou-Ku Chung , PhD 14 , Mark A. Turner , MRCPCH, PhD 16 , Lois E. H. Smith , MD, PhD 17 , Ann Hellström , MD, PhD 18 , on behalf of the study team
22 November 2018
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.
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 μg/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 μg/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.
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.
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.