A Multi-center, Double-Blind, Randomized, Two-Arm, Parallel-Group, Placebo Controlled Study to Assess the Efficacy and Safety of ELGN-2112 on Intestinal Malabsorption in Preterm Infants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Elgan Pharma Ltd.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

26 May 2025 → ongoing

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Elgan Pharma Ltd.

External identifiers

EU CT number

2024-517101-87-00

EudraCT number

2021-004890-29

ClinicalTrials.gov

NCT05670951

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To assess the efficacy of ELGN-2112 as compared to placebo on intestinal malabsorption in preterm infants as measured by number of days to achieve full enteral feeding*.

*Defined as first day of reaching three consecutive days of EN feeds ≥150 ml/kg/day.

Secondary objectives 19

1. To assess the effect of ELGN-2112 compared to placebo on the number of days to wean off PN (parenteral nutrition)
2. To assess the effect of ELGN-2112 compared to placebo on the incidence of severe Necrotizing Enterocolitis (NEC) (modified Bell’s stage grade ≥2a) in a pooled analysis of infants born at 26+0-28+6 weeks GA (FIT-PIV study) and infants born less than 26+0 weeks GA and Intra-Uterine Growth Restricted (IUGR) infants <3rd percentile (according to Fenton preterm growth chart) born at 26+0-31+6 weeks GA (FIT-05 study).
3. To assess the effect of ELGN-2112 compared to placebo on the Incidence of severe NEC (modified Bell’s stage ≥2a) in infants born at 26+0-28+6 weeks GA
4. To assess the effect of ELGN-2112 compared to placebo on the length of stay in the primary hospital
5. To assess the effect of ELGN-2112 compared to placebo on the distribution of severity of NEC according to modified Bell’s staging in a pooled analysis of infants born at 26+0-28+6 weeks GA (FIT-PIV study) and infants born less than 26+0 weeks GA and IUGR infants <3rd percentile born at 26+0-31+6 weeks GA (FIT-05 study)
6. To assess the effect of ELGN-2112 compared to placebo on the distribution of severity of NEC according to modified Bell’s staging in infants born at 26+0-28+6 weeks GA
7. To assess the effect of ELGN-2112 compared to placebo on the incidence of severe NEC (modified Bell’s stage ≥2a) in the entire study population
8. To assess the effect of ELGN-2112 compared to placebo on the distribution of severity of NEC according to modified Bell’s staging in the entire study population
9. To assess the effect of ELGN-2112 compared to placebo on the probability of reaching full enteral feeding at different time points
10. To assess the effect of ELGN-2112 compared to placebo on the number of days to achieve 120 ml/kg/day of enteral feeds
11. To assess the effect of ELGN-2112 compared to placebo on the probability of weaning off PN at different time points
12. To assess the effect of ELGN-2112 compared to placebo on growth of infants (Anthropometrics)
13. To assess the effect of ELGN-2112 compared to placebo on proportional contribution of EN and PN to total nutrition
14. To assess the effect of ELGN-2112 compared to placebo on the incidence of late-onset sepsis
15. To assess the effect of ELGN-2112 compared to placebo on the incidence of any of the adverse events of relevance (severe NEC, late-onset sepsis, death).
16. To assess the effect of ELGN-2112 compared to placebo on the number of days to discharge to home.
17. To assess the effect of ELGN-2112 compared to placebo on the incidence and severity of retinopathy of prematurity (ROP).
18. To compare the safety of ELGN-2112 to placebo up to 3 months CA (Part A).
19. To compare the safety of ELGN-2112 to placebo at 6, 12 and 24 months CA (Part B).

Conditions and MedDRA coding

Intestinal Malabsorption

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002116-PIP01-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Male or female preterm infants born at a gestational age 26+0 to 31+6 weeks. Gestational age matching (±2 weeks) between maternal dates and/or early antenatal ultrasound
2. Infant is expected to wean off parenteral nutrition (PN) at the primary hospital
3. Informed consent form signed by parent(s) or legal guardian
4. In the Investigator’s opinion, the infant is sufficiently stable to partake in the trial to completion
5. (France only) - only participants benefiting from a health insurance plan can participate in research
6. Birth weight ≥ 500 g
7. Singleton or twin birth
8. Postnatal age up through and including Day 5 (up to 120 hours post birth)
9. Fraction of inspired oxygen ≤ 0.60 at enrolment
10. Infant is cardiovascularly stable at time of enrolment and would be considered unstable if they require inotropic support
11. Infant is able to tolerate enteral feeds (defined as minimum of 10 ml/kg/day)

Exclusion criteria 14

1. Infant is consuming more than 80 ml/kg/day enterally at study entry
2. Infant is receiving pharmacological treatment for a hemodynamically significant PDA at the time of randomization
3. Heart and chest compression or any resuscitation drugs given to the infant during delivery
4. Subjects at risk for significant GI complications such as twin-to-twin transfusion syndrome (TTTS) or monochorionic monoamniotic twins
5. Participation in another interventional clinical study that may interfere with the results of this trial
6. Infant is not dependent on any parenteral amino acids/lipids as nutrition
7. Major congenital malformation (e.g., infants with genetic, metabolic, and/or endocrine disorder diagnosed before enrolment)
8. Intra-uterine growth restriction (IUGR) defined as weight for gestational age less than the third percentile according to Fenton preterm growth chart
9. Confirmed NEC
10. Maternal diabetes (Type I/II or gestational) requiring insulin during pregnancy or in mothers past medical history
11. Confirmed hyperinsulinemia or suspected hyperinsulinemia requiring glucose administration of more than 12 mg/kg/min at randomization
12. Any systemic insulin administration at randomization
13. Nothing per os (NPO) at study entry and enteral/oral supplements are not allowed
14. Hypersensitivity to any of the drug components- Recombinant Human Insulin (rh-Insulin), Maltodextrin, Sodium Chloride

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of days from treatment initiation to achieve full enteral feeding*, which is defined as the number of days to achieve enteral feeding of at least 150 ml/kg/day for three consecutive days during the treatment period *Defined as first day of reaching three consecutive days of EN feeds ≥150 ml/kg/day

Secondary endpoints 19

1. The number of days from treatment initiation to PN wean-off during the treatment period
2. Incidence of severe NEC (modified Bell’s stage ≥2a) by 40 weeks post-menstrual age (PMA) or discharge home, whichever is earlier, in infants born at 26+0-28+6 weeks GA (FIT-PIV study) and infants born less than 26+0 weeks GA and IUGR infants born at 26+0-31+6 weeks GA (FIT-05 study) as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986).
3. Incidence of severe NEC (modified Bell’s stage ≥2a) by 40 weeks PMA or discharge home, whichever is earlier, in infants born at 26+0-28+6 weeks GA as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986).
4. The number of days from treatment initiation to discharge from primary hospital
5. Distribution of severity of NEC by 40 weeks PMA or discharge home, whichever is earlier, in infants born at 26+0-28+6 weeks GA (FIT-PIV study) and infants born less than 26+0 weeks GA and IUGR infants born at 26+0-31+6 weeks GA (FIT-05 study) as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986) - pooled analysis
6. Distribution of severity of NEC by 40 weeks PMA or discharge home, whichever is earlier, according to modified Bell’s staging in infants born at 26+0-28+6 weeks GA as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986).
7. Incidence of severe NEC by 40 weeks PMA or discharge home, whichever is earlier, in the entire study population as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986).
8. Distribution of severity of NEC by 40 weeks PMA or discharge home, whichever is earlier, in the entire study population as assessed by central blinded reviewers and classified according to the “Modified Bell’s Staging Criteria for NEC” (Walsh-1986).
9. Percentage of infants reaching FEF for three consecutive days within 6, 8, and 10 days from treatment initiation
10. The number of days from treatment initiation to the first day the infant achieves EN volume of 120 ml/kg/day for three consecutive days during the treatment period
11. Percentage of infants weaned off PN within 4, 6, and 8 days from treatment initiation
12. Neonatal anthropometrics measurements during the treatment period and up to 3 months CA.
13. Percentage of EN and PN over total nutrition during the treatment period
14. Incidence of late onset sepsis (onset ≥72 hours after birth) by 40 weeks PMA or discharge home, whichever is earlier. Will be defined as either: a) culture proven late onset sepsis, OR b) clinically suspected culture negative late onset sepsis
15. Incidence of at least one of the adverse events of relevance by 40 weeks PMA or discharge home, whichever is earlier: • severe NEC (modified Bell’s stage ≥2a); • late-onset sepsis • death.
16. The number of days from treatment initiation to discharge to home
17. Incidence and severity of ROP up to 3 months CA according to the International Classification of Retinopathy of Prematurity (ICROP3)
18. Adverse Events (AEs) and Adverse Drug Reaction (ADRs); Blood glucose; Blood chemistry and haematology; Vital signs
19. Major morbidities (including cerebral palsy, severe vision and hearing loss and hospitalisation) at 6, 12 and 24 months CA; Anthropometrics measurements at 6, 12 and 24 months CA; Neurodevelopmental assessment at 24 months CA

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Elgan Pharma Ltd.

Sponsor organisation

Elgan Pharma Ltd.

Address

13 Wadi El Haj

City

Nazareth

Postcode

1603100

Country

Israel

Scientific contact point

Organisation

Elgan Pharma Ltd.

Contact name

Regulatory Department

Public contact point

Organisation

Elgan Pharma Ltd.

Contact name

Regulatory Department

Third parties 9

Locations

6 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications