Recombinant human (rh)IGF-1/rhIGFBP-3 for prevention of bronchopulmonary dysplasia

Abstract

Background: We conducted a phase 2 trial evaluating IGF-1 supplementation with rhIGF-1/rhIGFBP-3 for prevention of complications of prematurity. The primary endpoint of reduction in severity of retinopathy of prematurity was not met; however, improvements were seen in secondary endpoints, including bronchopulmonary dysplasia (BPD). Aims/Objectives: Secondary endpoint analysis to assess the effect of rhIGF-1/rhIGFBP-3 on BPD in extremely preterm infants. Methods: 121 infants born at gestational age 23w+0d to 27w+6d were randomized to rhIGF-1/rhIGFBP-3 (250µg/kg/day continuous IV infusion from birth to postmenstrual age 29w+6d) or standard care. BPD was defined by NICHD criteria and the physiologic definition. Target drug exposure was ≥70% IGF-1 values within normal intrauterine range (28‒109µg/L) and ≥70% intended duration of therapy. Results: The Full Analysis Set (FAS) included 61 infants on rhIGF-1/rhIGFBP-3 and 60 on standard care. 24/61 treated infants achieved target exposure (Evaluable Set; ES). rhIGF-1/rhIGFBP-3 reduced severe BPD by 53% in the FAS (44.9% standard care vs 21.3% treated) and 89% in the ES (44.9% vs 4.8%, Figure). In treated infants, trends were seen towards lower BPD severity with higher serum IGF-1. Conclusions: rhIGF-1/rhIGFBP-3 treatment in extremely preterm infants significantly decreased severe BPD. Reduction of BPD severity using rhIGF-1/rhIGFBP-3 is the primary endpoint in a planned phase 2b/3 trial.