Primary objective: To assess the efficacy of treatment with ELGN-2112 as compared to placebo on intestinal malabsorption in preterm infants as measured by the time to full enteral feeding. Defined as first day of reaching three consecutive days of…
ID
Source
Brief title
Condition
- Other condition
- Malabsorption conditions
Synonym
Health condition
Prematurity - preterm birth
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Numbers of days to achieve full enteral feeding, defined as the first day of
ability of the preterm infant to achieve enteral feeding of at least 150
ml/kg/day for three consecutive days.
Secondary outcome
1. Number of days until wean off PN
2. Incidence of Necrotizing Enterocolitis (NEC) (modified Bell*s stage grade
>=2a) in infants born at 26-28 weeks GA.
3. Number of days to discharge from primary hospital
4. Distribution of severity of NEC according to modified Bell*s staging in
infants born at 26-28 weeks GA.
5. Incidence of Necrotizing Enterocolitis (NEC) (modified Bell*s stage grade
>=2a) in the entire study population.
6. Distribution of severity of NEC according to modified Bell*s staging in the
entire study population.
7. Percentage of infants reaching full enteral feeding within 6, 8, and 10 days
from initiation of treatment.
8. Number of days to 120 ml/kg/day for three consecutive days
9. Percentage of infants weaned off PN within 4, 6, and 8 days from initiation
of treatment
10. Percent enteral/ parenteral feedings from total nutrition over time
11. Percentage of infants with sepsis
12. Percentage of subjects experiencing one of the adverse events of relevance
(NEC, Infections, Death)
13. Number of days to discharge to home
14. Anthropometrics
15. Retinopathy of prematurity (ROP) activity score at 30-36 weeks PMA
Background summary
Premature infants have an underdeveloped gastrointestinal tract at the time of
birth. As a result, nutritional intolerance is frequently seen, and these
infants are dependent on parenteral nutrition for a relatively long time.
However, there are also complications associated, such as sepsis or
cholestasis. Necrotizing enterocolitis is also a potential dreaded intestinal
complication. Breast milk - compared to formula - partly protects against these
complications. Various biologically active substances in breast milk protect
the premature neonate. One of these factors in breast milk is insulin, which
serves as a growth factor of the intestinal epithelium.
However, the insulin concentration in breast milk is particularly high in
colostrum; after a few days this concentration drops significantly, and after a
few days premature neonates hardly receive any insulin anymore.
Study objective
Primary objective:
To assess the efficacy of treatment with ELGN-2112 as compared to placebo on
intestinal malabsorption in preterm infants as measured by the time to full
enteral feeding. Defined as first day of reaching three consecutive days of EN
feeding >=150 ml/kg/day.
Secondary Objectives:
Secundaire doelstellingen:
1. Number of days until wean off PN
2. Incidence of Necrotizing Enterocolitis (NEC) (modified Bell*s stage grade
>=2a) in infants born at 26-28 weeks GA.
3. Number of days to discharge from primary hospital.
4. Distribution of severity of NEC according to modified Bell*s staging in
infants born at 26-28 weeks GA.
5. Incidence of Necrotizing Enterocolitis (NEC) (modified Bell*s stage grade
>=2a) in the entire study population.
6. Distribution of severity of NEC according to modified Bell*s staging in the
entire study population.
7. Percentage of infants reaching full enteral feeding within 6, 8, and 10 days
from initiation of treatment
8. Number of days to 120 ml/kg/day for three consecutive days
9. Percentage of infants weaned off PN within 4, 6, and 8 days from initiation
of treatment
10. Percent enteral/ parenteral feedings from total nutrition over time
11. Percentage of infants with sepsis
12. Percentage of infants experiencing one of the adverse events of relevance
(NEC, Infections, Death)
13. Number of days to discharge to home.
14. Anthropometrics
15. Retinopathy of prematurity (ROP) activity score at 30-36 weeks PMA.
Safety Objective:
To compare the safety of treatment of ELGN-2112 to placebo in preterm infants.
Study design
Multi-center, double-blind, randomized, two-arm, parallel-group,
placebo-controlled.
The study physician will follow a recommended feeding protocol. The final
feeding scheme is subject to the physician*s clinical evaluation.
Screening procedures:
After the parents or guardian signs the Informed Consent Form (ICF), all
inclusion/exclusion criteria will be checked for eligibility. A complete
medical history and physical examination will be performed. Within 24 hours of
the screening procedures, eligible infants will be randomly assigned to one of
the two treatment groups.
Treatment procedure:
During the treatment period, the infants will receive study medication with
their enteral feeding until discharge from the hospital or up to 28 days,
whichever occurs first. The daily drug dose will be administered preferably
divided over at least four times each day with enteral feedings. Treatment
should commence at postnatal age of up through and including Day 5 (up to 120
hours post birth).
Follow up period:
The infants will return to the clinical site for a follow-up visit at 6 months,
12 months, and 24 months corrected age and 6 years. If additional follow up
visits take place as standard-of-care, these will be recorded as well (up to
age 12). Unblinding will take place 1 year after randomization of last subject.
Intervention
The study will be comprised of 180 infants per arm, in two strata (26+0-28+6
& 29+0-32+0 GA) or at least 360 infants in all, with at least 140 (70 per
arm) in the younger strata. Each infant will be randomly assigned in a 1:1
ratio to the study medication (ELGN-2112) or placebo. In the event of twin
pregnancies, if both twins are eligible to be included in the study, the
firstborn will be randomized, and the other sibling will be automatically
allocated to the same treatment group as the firstborn.
Study burden and risks
Except for the risks already mentioned in E9 no ther risks are foreseen. The
additional burden comparded to standard of care is minimal.
13 Wadi El Haj 13 Nazareth 13
Nazareth 13
IL
13 Wadi El Haj 13 Nazareth 13
Nazareth 13
IL
Listed location countries
Age
Inclusion criteria
1. Male or female preterm infant 26 and up to 32 weeks gestation (32 weeks + 0
day maximum). Gestational age matching (±2 weeks) between maternal dates and/or
early antenatal ultrasound * 2. Birth weight >= 500 g 3. Singleton or twin birth
4. Postnatal age up through and including Day 5 (up to 120 hours post birth) 5.
Fraction of inspired oxygen <= 0.60 at enrolment 6. Infants must demonstrate
cardiovascular stability at time of enrolment and would be considered unstable
if they require blood pressure support via a central line 7. Infant is able to
tolerate enteral feeds 8. Infant is expected to wean off parenteral nutrition
(PN) at the primary hospital 9. Informed consent form signed by parents or
legal guardian 10. In the Investigator*s opinion, the infant is sufficiently
stable to partake in the trial to completion * If both exist and difference
> 2 weeks, based on early antenatal ultrasound
Exclusion criteria
1. Infant is consuming more than 100 ml/kg/day enterally at study entry
2. Infant is not dependent on any parenteral amino acids/lipids as nutrition
3. Major congenital malformation (e.g., infants with genetic, metabolic, and/or
endocrine disorder diagnosed before enrolment)
4. Intra-uterine growth restriction (IUGR) defined as either weight for
gestational age less than the third percentile according to Fenton preterm
growth chart.
5. Confirmed necrotizing enterocolitis (NEC)
6. Maternal diabetes (Type I/II or gestational) requiring insulin during
pregnancy or in mothers past medical history.
7. Suspected or confirmed hyperinsulinemia requiring glucose administration of
more than 12 mg/kg/min at randomization.
8. Any systemic insulin administration at randomization.
9. Nothing per os (NPO) at study entry and enteral/oral supplements are not
allowed.
10. Heart and chest compression or any resuscitation drugs given to the infant
during delivery
11. Subjects at risk for significant GI complications such as twin-to-twin
transfusion syndrome (TTTS) or monochorionic monoamniotic twins.
12. Participation in another interventional clinical study that may interfere
with the results of this trial**
13. Hypersensitivity to any of the drug components- Recombinant Human Insulin
(rh-Insulin), Maltodextrin, Sodium Chloride
** Participation in another interventional clinical study that may interfere
with results of this trial is not allowed until discharge from the hospital
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-004890-29-NL |
| ClinicalTrials.gov | NCT05670951 |
| CCMO | NL82850.018.22 |