A Study of 2-Iminobiotin in Neonates With Perinatal Asphyxia

NCT01626924 | Terminated Phase 2 DMC

• 2 other identifiers: NEU 01-02-012011-002502-74
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Perinatal Asphyxia

Keywords

Perinatal Asphyxia; Neonatal encephalopathy; Oxygen shortage at birth; Antenatal asphyxia; hypoxia-ischaemia; birth asphyxia; asphyxia neonatorum

Outcome Measures

Primary Outcomes (2)

• The Lac/NAA ratio in the basal ganglia as measured by single or multiple voxel Magnetic Resonance Spectroscopy (MRS).

  Proton (1H) MRS of the basal ganglia lactate/N-acetyl aspartate (Lac/NAA) peak-area ratio is considered to be an accurate quantitative biomarker for prediction of neurodevelopmental outcome after Neonatal Encephalopathy (Thayyil et al, 2010). Results will be compared between arms.

  The MRS will be performed between 3-7 days after birth

• The composite endpoint of survival at 48h with a normal aEEG

  Electrocortical brain activity is measured by aEEG, starting as soon as possible after birth and before study medication has been initiated and continued until at least 72h after start of treatment. Every 4h the background pattern of the aEEG and the presence of seizures will be recorded in the eCRF. The aEEG will be classified as normal or abnormal at 48h after the start of treatment. Hence, for this primary endpoint, a good outcome is defined as survival in combination with a normal aEEG at 48h. A bad outcome is either death or abnormal aEEG at 48h after start treatment.

  48h after start treatment

Secondary Outcomes (13)

• MRI: pattern of injury score

  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

  The MRI will be performed between 3-7 days after birth

• aEEG. Background pattern

  Every 4 hours until 48 hours after start treatment

• Mortality

  first 7 days after birth

• Length of stay at the level III NICU

  On the average this is expected to be 4-14 days after birth

Study Arms (1)

2-Iminobiotin

EXPERIMENTAL

Drug: 2-Iminobiotin

Interventions

2-Iminobiotin DRUG

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.

2-Iminobiotin

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• 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.
• Presence in hospital and ability to start treatment within 6h after birth.
• Informed Consent Form signed before first study-related activity according to local law.
• Receiving standard therapy without hypothermia.

You may not qualify if:

• Major antenatally known- or congenital abnormalities, such as hernia diaphragmatica requiring ventilation.
• Major antenatally known chromosomal abnormalities, such as trisomy 13 or 18 or neonates with evident syndromal appearances including brain dysgenesis.
• Severe growth restriction with a birth weight below the 3rd percentile.
• Inability to insert an indwelling catheter (umbilical venous catheter or percutaneously inserted central catheter, preferably multiple lumen).

Sponsors & Collaborators

• Neurophyxia B.V.: lead

Study Sites (2)

T.R. Ministry of Health Izmir Tepecik Training and Research Hospital

Izmir, 35540, Turkey (Türkiye)

Location

Yıl University Medical Faculty Hospital

Van, 65080, Turkey (Türkiye)

Location

Related Publications (1)

• Peeters-Scholte C, Koster J, Veldhuis W, van den Tweel E, Zhu C, Kops N, Blomgren K, Bar D, van Buul-Offers S, Hagberg H, Nicolay K, van Bel F, Groenendaal F. Neuroprotection by selective nitric oxide synthase inhibition at 24 hours after perinatal hypoxia-ischemia. Stroke. 2002 Sep;33(9):2304-10. doi: 10.1161/01.str.0000028343.25901.09.

  PMID: 12215603 BACKGROUND

MeSH Terms

Conditions

Asphyxia Neonatorum

Interventions

2-iminobiotin

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Paul Leufkens, PharmD

  Neurophyxia B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2012
• First Posted: June 25, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: March 1, 2016
• Last Updated: May 25, 2017

Record last verified: 2017-05

Locations

TU (2)