A Study of 2-Iminobiotin in Neonates With Perinatal Asphyxia

NCT ID: NCT01626924

Last Updated: 2017-05-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2016-03-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

2-Iminobiotin

Group Type: EXPERIMENTAL

2-Iminobiotin

Intervention Type: 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.

Interventions

2-Iminobiotin

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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Maximum Eligible Age: 6 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Neurophyxia B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul Leufkens, PharmD

Role: STUDY_DIRECTOR

Neurophyxia B.V.

Locations

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

Izmir, , Turkey (Türkiye)

Yıl University Medical Faculty Hospital

Van, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

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.

Reference Type: BACKGROUND

PMID: 12215603 (View on PubMed)

Other Identifiers

2011-002502-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NEU 01-02-01

Identifier Type: -

Identifier Source: org_study_id