Efficacy and Safety of ELGN-2112 in Treating Intestinal Malabsorption in Preterm Infants: A Double-Blind, Randomized, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of ELGN-2112 compared to placebo in addressing **intestinal malabsorption** in preterm infants. This is clinically relevant as it focuses on the time required to achieve full enteral feeding, defined as reaching three consecutive days of enteral nutrition (EN) feeds at a volume of ≥150 ml/kg/day. Achieving full enteral feeding is crucial for the nutritional management and growth of preterm infants, potentially reducing the need for parenteral nutrition (PN) and associated complications.

Secondary objectives include assessing the effect of ELGN-2112 compared to placebo on various clinical outcomes:

• Number of days to wean off PN.
• Incidence and severity of severe **Necrotizing Enterocolitis** (NEC) using modified Bell’s staging in different infant populations.
• Length of stay in the primary hospital and number of days to discharge to home.
• Probability of reaching full enteral feeding and weaning off PN at different time points.
• Growth of infants as measured by anthropometrics.
• Proportional contribution of EN and PN to total nutrition.
• Incidence of late-onset sepsis and any adverse events of relevance, including severe NEC, late-onset sepsis, and death.
• Incidence and severity of **retinopathy of prematurity** (ROP).
• Safety comparison of ELGN-2112 to placebo up to 3 months corrected age (CA) and at 6, 12, and 24 months CA.

The clinical trial involves a total of **185 participants** who are preterm infants diagnosed with **intestinal malabsorption**. The study population includes both male and female infants born at a gestational age between 26+0 to 31+6 weeks. Participants are required to be cardiovascularly stable and able to tolerate enteral feeds, with a birth weight of at least 500 grams. The trial includes infants who are either singletons or twins, with a postnatal age of up to 5 days. The selection criteria ensure that the infants are expected to wean off parenteral nutrition at the primary hospital and have a fraction of inspired oxygen of 0.60 or less at enrollment. The trial population was selected based on these criteria, and informed consent was obtained from the parents or legal guardians. The study focuses on a vulnerable population, emphasizing the need for careful monitoring and ethical considerations throughout the trial.

The clinical trial is designed as a **randomized**, double-blind, two-arm, parallel-group, placebo-controlled study to evaluate the efficacy and safety of ELGN-2112 in preterm infants with **intestinal malabsorption**. The primary objective is to assess the efficacy of ELGN-2112 compared to placebo, specifically measuring the number of days required to achieve full enteral feeding, defined as three consecutive days of enteral nutrition feeds of at least 150 ml/kg/day. The trial is expected to commence recruitment on March 3, 2025, and conclude by February 28, 2033.

Participants will be preterm infants born between 26+0 to 31+6 weeks of gestation, who are cardiovascularly stable, able to tolerate enteral feeds, and expected to wean off parenteral nutrition at the primary hospital. The study will involve multiple visits, starting with a screening visit to confirm eligibility based on inclusion criteria such as gestational age, birth weight, and postnatal age. Following randomization, participants will receive either the investigational product, ELGN-2112, or a placebo via an enteral feeding tube. The treatment period will last up to 28 days, with regular follow-up visits to monitor progress and collect data on primary and secondary endpoints.

Secondary endpoints include the time to wean off parenteral nutrition, incidence of severe necrotizing enterocolitis (NEC) by 40 weeks post-menstrual age or discharge, and other relevant clinical outcomes. The study will also assess the incidence of adverse events, including late-onset sepsis and retinopathy of prematurity. Participants will be involved in the study for the duration of the treatment period and follow-up assessments, with conditions for early termination including significant adverse events or withdrawal of consent by the parent or legal guardian.

The clinical trial involves the evaluation of **ELGN-2112**, an **oral solution** containing **insulin human** as the active substance. This investigational product is administered via an **enteral feeding tube**. The dosage is specified as a maximum of 0.3 IU/kg per day, with the total dose not exceeding 0.3 IU/kg over the treatment period. The maximum treatment duration is 28 days. The formulation is designed for pediatric use, specifically targeting preterm infants with intestinal malabsorption. The product is developed by ELGAN PHARMA LTD. and is classified as an orphan drug under the designation EU/3/15/1532.

The study also includes a **placebo** control, which is a **powder for reconstitution** intended for enteral administration. The placebo is used to maintain the double-blind nature of the trial, ensuring unbiased assessment of the investigational product's efficacy and safety. The placebo is administered in a manner consistent with the experimental treatment to ensure comparability between the study arms. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The efficacy of the investigational product ELGN-2112 in the clinical trial will be assessed by evaluating its impact on **intestinal malabsorption** in preterm infants. The primary endpoint for efficacy is the number of days from treatment initiation to achieve full enteral feeding, defined as reaching enteral feeding of at least 150 ml/kg/day for three consecutive days. This measurement will be collected during the treatment period.

Secondary endpoints include the number of days from treatment initiation to wean off parenteral nutrition, incidence of severe necrotizing enterocolitis (NEC) by 40 weeks post-menstrual age or discharge home, and the number of days from treatment initiation to discharge from the primary hospital. The incidence and distribution of NEC severity will be assessed using the Modified Bell's Staging Criteria, with evaluations conducted by central blinded reviewers. Additional secondary endpoints involve the percentage of infants reaching full enteral feeding within specified timeframes, neonatal anthropometric measurements, and the incidence of late-onset sepsis.

Data collection will occur at various timepoints throughout the treatment period, with specific assessments aligned with the defined endpoints. The analysis will involve comparing the outcomes between the treatment and placebo groups to determine the efficacy of ELGN-2112 in improving intestinal malabsorption in the target population.