IGF-1/IGFBP3 Prevention of Retinopathy of Prematurity

ROP was measured by central exams with fundus photography. Maximum severity of ROP stage across all retinal examinations included International Classification of Retinopathy of Prematurity, a 5 stage system, for the classification of ROP with 7 different outcomes of the ROP stage in each retinal examination: 0, 1, 2, 3, 3+, 4, and 5. This is an ordinal scale with higher numbers indicating a more severe outcome. The maximum severity of ROP across all time points was assessed from 31 PMA weeks up to 40 PMA Weeks +/- 4 days (end of study).

Severity of BPD as mild, moderate and severe were based on the National Institute of Child Health and Human Development (NICHD) guidelines for preterm infants born at gestational age (GA) less than (<) 32 weeks. Mild: oxygen requirement during the first 28 days but in room air at PMA 36 weeks or discharge to home, whichever comes first. Moderate BPD: oxygen requirement during the first 28 days and oxygen <30 percent (%) at PMA 36 weeks or discharge to home, whichever comes first. Severe BPD: oxygen requirement during the first 28 days and oxygen greater than equal (≥)30% through head hood or nasal canula, or continuous positive airway pressure, or mechanical ventilation, or high flow nasal cannula ≥2 L/min at PMA 36 weeks or discharge to home, whichever comes first.

The rate of change is the rate of specific body weight change per day in kilogram (kg).

The rate of change is the length change per day in centimeter (cm).

The rate of change is the head circumference change per day in centimetre (cm).

Brain volume was measured using cerebral magnetic resonance imaging (MRI). Brain volume included cerebrospinal volume, gray matter volume, white matter volume, and total cerebellar volume

Development of intraventricular hemorrhage was assessed by cerebral ultrasound and coded as a binary endpoint (presence or absence of IVH).

Integration of the maximum severity of ROP stage and the duration of the time interval with respect to each retinal examination. AUC for the maximum severity of ROP was calculated using the trapezoidal rule. The area between each 2 visits was calculated by multiplying the average of the maximum severities of the 2 visits by the difference in days and analyzed using the van Elteren test. ROP is classified according to the International Classification and is subdivided into 5 stages (1-5) with higher values representing greater severity.

ROP was measured by central exams with fundus photography. Maximum severity of ROP stage across all retinal examinations included International Classification of Retinopathy of Prematurity, a 5 stage system, for the classification of ROP with 7 different outcomes of the ROP stage in each retinal examination: 0, 1, 2, 3, 3+, 4, and 5. This is an ordinal scale with higher numbers indicating a more severe outcome.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse event was defined as the onset of any AE or if the severity of a pre-existing AE worsened any time on or after the date of first dose of investigational product.

Serum samples were collected from treated and control participants for quantification of IGF-1 using validated immunoassays. Target range of serum IGF-1 was 28-109 mcg/L. The percentage of serum IGF-1 levels across treated participants that fall within the range was reported.