Primary objective: To compare the safety of treatment with ELGN-2112 to placebo in preterm infants born less than 26 weeks GA and IUGR infants<3rd percentile * born at 26-32 weeks GA. * According to Fenton preterm growth chart. Secondary…
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
Safety of ELGN-2112 as compared to placebo in preterm infants born under 26
weeks GA and IUGR infants born between 26-32 weeks GA.
Secondary outcome
1. Number 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.
2. Incidence of Necrotizing Enterocolitis (NEC) (Incidence of modified Bell*s
stage grade >=2a of NEC)
3. Number of days until wean off PN (total cessation)
4. Distribution of severity of NEC according to modified Bell*s staging
5. Number of days to 120 ml/kg/day for three consecutive days
6. Percentage of infants reaching full enteral feeding at time points of
interest from initiation of treatment.
7. Percentage of infants weaned off PN at time points of interest from
initiation of treatment
8. Percent enteral/ parenteral feedings from total nutrition over time
9. Percentage of infants with sepsis
10. Percentage of subjects experiencing one of the adverse events of relevance
(NEC, Infections, Death)
11. Number of days to discharge from primary hospital.
12. Number of days to discharge home.
13. Anthropometrics
14. 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 compare the safety of treatment with ELGN-2112 to placebo
in preterm infants born less than 26 weeks GA and IUGR infants<3rd
percentile * born at 26-32 weeks GA. * According to Fenton preterm growth
chart. Secondary objectives: 1. 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 2. To assess the
effect of ELGN-2112 on Incidence of Necrotizing Enterocolitis (NEC) (modified
Bell*s stage grade >=2a) 3. To assess effect of ELGN-2112 compared to placebo on
number of days until full wean off PN (total cessation) 4. To assess the effect
of ELGN-2112 on Distribution of severity of NEC according to modified Bell*s
staging 5. To assess the effect of ELGN-2112 on Number of days to 120 ml/kg/day
for three consecutive days. 6. To assess the effect of ELGN-2112 on percentage
of infants reaching full enteral feeding at time points of interest from
initiation of treatment. 7. To assess the effect of ELGN-2112 on percentage of
infants weaned off PN at time points of interest from initiation of treatment
8. To assess the effect of ELGN-2112 on Percent enteral/ parenteral feedings
from total nutrition over time. 9. To assess the effect of ELGN-2112 on
Percentage of infants with sepsis 10. To assess the effect of ELGN-2112 on
Percentage of infants experiencing one of the adverse events of relevance (NEC,
Infections, Death). 11. To assess the effect of ELGN-2112 on Number of days to
discharge from primary hospital 12. To assess the effect of ELGN-2112 compared
to placebo on number of days to discharge home. 13. To assess the effect of
ELGN-2112 on Anthropometrics 14. To assess the effect of ELGN-2112 on
Retinopathy of prematurity (ROP) activity score at 30-36 weeks PMA.
Study design
This basket study will evaluate the safety of ELGN-2112 as compared to placebo
in several populations of interest.
ELGN-2112 is a powder for reconstitution containing human recombinant insulin,
reconstituted in breast milk, infant formula, water, or normal and half-normal
saline, and administered concomitantly with preterm infant's enteral nutrition
for local gastrointestinal (GI) therapy.
The study will enroll preterm infants born under 26 weeks gestational age and
Intra-Uterine Growth Restricted (IUGR) infants (below 3rd percentile*), born at
26-32 weeks GA , weighing at least 450 g who meet the inclusion and exclusion
criteria.
Safety will be assessed by capturing of adverse events (AEs), PE, and vital
signs during the treatment period.
The effect on intestinal malabsorption will be evaluated by comparing the
ability of preterm infants to achieve full enteral (EN) feeding for three
consecutive days.
Subjects will be treated for 42 days (6 weeks) or up to hospital discharge,
whichever is the earliest. They will receive ELGN-2112 treatment according to
their recorded weight (0.3IU/kg/day) or placebo.
During the treatment period, infants will undergo daily evaluation of AEs,
concomitant medication, nutrition, general growth, and development progression.
Infants will be evaluated at day of discharge. Follow-up visits will be
performed at 6 months, 12 months, and 24 months corrected age, and 6 years.
Intervention
Following screening procedures eligible infants will be randomly assigned to
one of the two groups in a 1:1 ratio. Randomization should take place as close
as possible to treatment initiation and within 24 hours of confirmation of
eligibility.
Randomization will be balanced per country within each of the following:
• Preterm infants born less than 26 weeks GA (up to 25+6)
• Intra-Uterine Growth Restricted (IUGR) infants (below 3rd percentile), born
between 26+0 to 28+6 GA.
• Intra-Uterine Growth Restricted (IUGR) infants (below 3rd percentile), born
between 29+0 to 31+6 GA.
Randomization of infants (or, in the case of twins, families) within stratum,
to arm A or B will be in a 1:1
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.
Wadi El Haj 13
Nazareth 13
IL
Wadi El Haj 13
Nazareth 13
IL
Listed location countries
Age
Inclusion criteria
1. Male or female preterm infant born less than 26 weeks GA (up to 25+6) or
Intra-Uterine Growth Restricted (IUGR) infants (below 3rd percentile), born
between 26+0 to 31+6 GA. *Gestational age matching (±2 weeks) between maternal
dates and/or early antenatal ultrasound. 2. Birth weight >= 450g 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. For infants born under 26 weeks GA, Intra-uterine growth restriction (IUGR)
defined as 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. 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 the 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 | EUCTR2022-004195-42-NL |
| CCMO | NL83530.018.23 |