Perinatal asphyxia MedDRA version: 14.1 Level: LLT Classification code 10004943 Term: Birth asphyxia System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders MedDRA version: 14.1 Level: LLT Classification code 10003500 Term: Asphyxia neonatal System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Neurophyxia B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following requirements prior to inclusion in the study: 1. Neonates with = 36 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting one or more of the following criteria cannot be included 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide an early evaluation of the efficacy using magnetic resonance spectroscopy [MRS] and the combination of survival with amplitude-integrated electroencephalogram [aEEG]) of 2-IB ;Secondary Objective: • To evaluate the short term safety and tolerability of 2-IB; • To evaluate the pharmacokinetic profile of 2-IB; • To gather preliminary evidence on the long term efficacy of 2-IB, as measured by neurodevelopmental outcome at 24 months after birth; • To gather preliminary evidence on the long term safety of 2-IB, as measured by serious adverse events reports up to 24 months after birth. ;Primary end point(s): Primary efficacy parameters as assessed by the Medical Adjudication Committee: • The Lac/NAA ratio in the basal ganglia as measured by single or multiple voxel 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). • 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 CRF. The aEEG will be classified as normal or abnormal at 48h after the start of treatment. The aEEG will be scored in five categories using pattern-recognition (Hellstrom-Westas et al, 2006): continuous normal voltage (CNV) and discontinuous normal voltage (DNV) being classified as normal (Thoresen et al, 2010), and burst suppression (BS), continuous extremely low voltage (CLV) and flat trace (FT) classified as abnormal. To prevent bias due to death before 48h after start treatment, survival is added as parameter. Hence, for this primary endpoint, a good outcome is defined as surviv | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy parameters • MRI: pattern of injury score Neuro-imaging by Magnetic Resonance Imaging (MRI) between 3 and 7 days following birth. The scoring system used is the pattern of injury score (Rutherford et al, 2010 appendix) in 4 areas of the brain (cortex, basal ganglia and thalamus, white matter and posterior limb of the internal capsule (PLIC)). Abnormal MRI is reported to be a predictor of poor outcome when at least one of following occurs (Rutherford et al, 2010): o Moderate or severe score in basal ganglia and thalamus o Abnormal PLIC o Severe white matter abnormalities • MRI: DWI (diffusion weighted images): apparent diffusion coefficient (ADC) in basal ganglia and PLIC • aEEG. Additional parameters derived from the aEEG recording will be assessed: o aEEG at 36h after start of study drug administration (classified the same way as described for the primary endpoint at 48h) o aEEG at 4-hour intervals until 48h after start of study drug administration (classified the same way as de described for the primary endpoint at 48h) o Time to normal aEEG, defined as the first time a normal aEEG is seen after birth o Time until the aEEG shows sleep-wake-cycling (Osredkar et al, 2005) o Presence of (sub)clinical seizures (Glass et al, 2009, Bjorkman, 2010) • Full neurological examination at discharge from level III NICU (see Table 4) • Mortality during first 7 days after birth • Length of stay at the level III NICU Safety parameters: vital signs, clinical laboratory parameters, clinical evaluation and adverse events and local tolerance. Pharmacokinetic parameters to be determined include • Cmax (observed maximum plasma concentration) • AUC0-4h (area under the plasma concentration-time curve from time 0 to 4h after administration) • AUC0-8 (area under the plasma concentration-time curve from time 0 to infinity) • Tend of infusion (time at maximum plasma concentration). • t1/2 (terminal elimination half-life) | — |
Countries
Georgia, Lithuania, Romania, Turkey
Contacts
Public ContactVP regulatory and medical affairs
Neurophyxia B.V.
Outcome results
None listed