This trial is active, not recruiting.

Condition perinatal asphyxia
Treatment 2-iminobiotin
Phase phase 2
Sponsor Neurophyxia B.V.
Start date June 2012
End date October 2014
Trial size 6 participants
Trial identifier NCT01626924, 2011-002502-74, NEU 01-02-01


In case of insufficient oxygen supply to the brain of a newborn child (perinatal asphyxia), toxic compounds will be formed. These toxic compounds will damage the cells of the brain. 2 Iminobiotin (2 IB) is an investigational medicinal product that is related to vitamin B7. From studies in animals it has been shown that 2-IB may prevent the formation of the toxic compounds. Also it has been shown to be safe in in studies in juvenile animals and in healthy, adult male volunteers. The doctors hope that this will prevent (part of) the potential brain damage that may result from lack of oxygen to the brain.

This study is the first study in the target population: newborn with moderate to severe oxygen shortage during birth. In this study the investigators evaluate short term efficacy, safety and pharmacokinetics of 2-Iminobiotin. In the follow-up phase the investigators evaluate the long term efficacy and safety.

The study hypothesis is that 2-Iminobiotin will help to decrease the brain damage after oxygen shortage and is indeed safe. The brain damage will be measured both in the first week and during the first two years of life. The study was designed as a study with two parts an open label pilot part (6 patients) and a double-blind randomised part (60 patients). Due to lack of recruitment it was decided in September2014 to stop recruitment after the open label pilot part of the study (6 patients).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
2-Iminobiotin is formulated as a 0.75 mg/ml isotonic, iso-osmotic, saline solution with a pH of 4. It is administered as a solution for I.V.infusion through a central catheter. Six pulse doses will be given in 20 hours. Dosage will starts with 0.2 mg/kg/dose, but may be adapted during the study.

Primary Outcomes

The Lac/NAA ratio in the basal ganglia as measured by single or multiple voxel Magnetic Resonance Spectroscopy (MRS).
time frame: The MRS will be performed between 3-7 days after birth
The composite endpoint of survival at 48h with a normal aEEG
time frame: 48h after start treatment

Secondary Outcomes

MRI: pattern of injury score
time frame: The MRI will be performed between 3-7 days after birth
MRI: DWI (diffusion weighted images): apparent diffusion coefficient (ADC) in basal ganglia and PLIC
time frame: The MRI will be performed between 3-7 days after birth
aEEG. Background pattern
time frame: Every 4 hours until 48 hours after start treatment
time frame: first 7 days after birth
Length of stay at the level III NICU
time frame: On the average this is expected to be 4-14 days after birth
Neurodevelopmental status
time frame: 3,6,12,18 and 24 months after treatment
Long term safety
time frame: 3,6,12,18,24 months
Safety during hospitalization period
time frame: Participants will be followed up for the duration of stay at hospital after birth (hospitalization period), on the average this will be 2-4 weeks
Pharmacokinetics during the treatment phase
time frame: From start of treatment untill right after last treatment has been given (20h15min after start treatment)
Neurological status as assessed by full neurological examination
time frame: at discharge from level III NICU on the average this will 7-14 days after birth.
aEEG. Time to normal aEEG
time frame: Up to 72 hours after start treatment
aEEG. Seizures (clinical and sub-clinical)
time frame: 48 hours after start treatment
aEEG. Time to normal sleep-wake cycling
time frame: up to 72 hours after start treatment

Eligibility Criteria

Male or female participants up to 6 hours old.

Inclusion Criteria: 1. Neonates with ≥ 36 and <44 weeks gestation with at least one of the following: - Apgar Score ≤ 5 at 10 minutes after birth - Continued need for resuscitation, including endotracheal or mask ventilation at 10 minutes after birth - Acidosis, defined as either umbilical cord pH or any arterial, venous, capillary pH within 60 minutes of birth pH ≤ 7.00 - Acidosis, defined as base deficit ≥ 16 mmol/l in umbilical blood sample or any blood sample within 60 minutes of birth (arterial or venous). 2. The presence of moderate/severe encephalopathy defined as: - Altered state of consciousness (lethargy, stupor, coma) and at least one of the following: - Hypotonia - Abnormal reflexes including oculomotor or papillary abnormalities - Weak or absent suck reflex - Clinical seizures AND - Depression of the background pattern (lower margin≤ 5 µV meaning at least DNV or BS, CLV, FT) or the presence of seizure activity on the aEEG, registered for at least 30 minutes within 6h after birth. 3. Presence in hospital and ability to start treatment within 6h after birth. 4. Informed Consent Form signed before first study-related activity according to local law. 5. Receiving standard therapy without hypothermia. Exclusion Criteria: 1. Major antenatally known- or congenital abnormalities, such as hernia diaphragmatica requiring ventilation. 2. Major antenatally known chromosomal abnormalities, such as trisomy 13 or 18 or neonates with evident syndromal appearances including brain dysgenesis. 3. Severe growth restriction with a birth weight below the 3rd percentile. 4. Inability to insert an indwelling catheter (umbilical venous catheter or percutaneously inserted central catheter, preferably multiple lumen).

Additional Information

Official title A Multi-centre, Randomised, Double-blind, Placebo-controlled Phase II Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of 2-Iminobiotin (2-IB) in Neonates With ≥36 Weeks GA With Moderate to Severe Perinatal Asphyxia
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Neurophyxia B.V..