Study of NNZ-2566 in Patients With Traumatic Brain Injury Under EFIC

Study Overview
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Brief Summary
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The purpose of this study is to determine whether NNZ-2566 is safe and effective in the treatment of Traumatic Brain Injury (TBI).

Detailed Description
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Moderate to severe traumatic brain injury frequently results in persistent problems with memory, attention span, mood and more complex brain functioning such as planning and organizing. There are currently no drugs available to reduce the brain damage or the persisting symptoms that result from TBI. The longer term goal of this study is to provide physicians with a safe and effective treatment for TBI

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Study of NNZ-2566 in Patients With Traumatic Brain Injury (TBI) Conducted Under an Exception From Informed Consent (EFIC)

Conditions
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Brain Injuries

Intervention / Treatment
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* Drug: NNZ-2566
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-penetrating TBI. Age 16-75 years. Admission to hospital. Post resuscitation GCS 4-12. Have at least one reactive pupil. Able to receive investigational product within 8 hours of injury. Hemodynamically stable after resuscitation (systolic blood pressure (SBP) >100 mm Hg). Able to read and write English and have sufficient motor dexterity prior to injury to undertake the neuropsychological and activities of daily living (ADL) testing, in the opinion of the investigator, at 1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks) post injury. Exclusion Criteria: Penetrating brain injury. Spinal cord injury. Presence or known history of prior cerebral injury requiring hospitalization that would, in the opinion of the Investigator, interfere with or bias the assessment of efficacy. Non-traumatic brain injury. Known history of any medical or psychiatric disorder, or any severe concomitant disease that would, in the opinion of the Investigator, interfere with or bias the assessment of efficacy. Significant non-central nervous system (CNS) injuries sustained at the time of the TBI would, in the opinion of the Investigator, interfere with or bias the assessment of efficacy. Weight >150 kg. Participation in another clinical trial within the previous 4 weeks. Clinical state requiring greater than 6 L blood, colloid or crystalloid fluid resuscitation prior to randomization. Pregnant or nursing mothers. Women of child-bearing potential must have a negative urine or blood test prior to randomization. Prior enrollment in this study. QTc Exclusions. The study will use the exclusion criteria as defined in ICH Guideline E14 to exclude patients with a risk of QT/QTc prolongation, as follows: A marked baseline prolongation of corrected QT/QTc interval >450 ms. History of risk factors for torsade de pointes (e.g. heart failure, hypokalemia (serum potassium at screening <3.0 mmol/L)or family history of long QT syndrome).

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NNZ-2566<br>20 mg/kg intravenous bolus infusion of NNZ-2566 over 10 minutes followed by a continuous intravenous infusion of 6 mg/kg/h (n=133) intravenous infusion of NNZ-2566 for a total of 72 consecutive hours. | Drug: NNZ-2566<br>* Solution for intravenous infusion. Intravenous bolus infusion over 10 minutes followed by a continuous intravenous maintenance infusion for a total of 72 consecutive hours.<br>* Other names: Glycyl-L-2-Methylprolyl-L-Glutamic Acid;|
| Placebo Comparator: Sodium Chloride (0.9%) for Injection<br>Intravenous bolus infusion of Sodium Chloride (0.9%) for Injection over 10 minutes followed by a continuous intravenous infusion of Sodium Chloride (0.9%) for Injection for a total of 72 consecutive hours. | Drug: Placebo<br>* Sodium Chloride 0.9% Injection<br>* Other names: Sodium Chloride 0.9% Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs) |  | AEs to discharged or Day 30 post randomization, whichever occurs first, and SAEs through to 3 months (defined as 12-14 weeks), post randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of efficacy in modifying global outcomes by evaluating Glasgow Outcome Scale - Extended (GOS-E) and activities of daily living (Mayo-Portland Adaptability Inventory - 4th Edition (MPAI-4)) |  | 1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization. | 
| Improvement in cognitive and neuropsychological functioning. |  | 1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization. | 
| Modification of the acute physiological processes in TBI by evaluating electroencephalographic (EEG) determinants in patients with moderate to severe TBI (defined as GCS 4-12), and biomarker levels. |  | Baseline through to 72 hours post-start of infusion. | 
| Blood pharmacokinetics (PK) of an intravenous (i.v) dose of NNZ-2566 when administered as a 10-minute infusion immediately followed by a 72-hour infusion. |  | Start of infusion through to 12 hours post infusion. |