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)

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

Sponsors

Lead sponsor: Neuren Pharmaceuticals Limited

Source Neuren Pharmaceuticals Limited
Brief Summary

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

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

Overall Status Completed
Start Date February 2013
Completion Date January 2016
Primary Completion Date January 2016
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure 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
Measure 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.
Enrollment 261
Condition
Intervention

Intervention type: Drug

Intervention name: NNZ-2566

Description: Solution for intravenous infusion. Intravenous bolus infusion over 10 minutes followed by a continuous intravenous maintenance infusion for a total of 72 consecutive hours.

Arm group label: NNZ-2566

Other name: Glycyl-L-2-Methylprolyl-L-Glutamic Acid

Intervention type: Drug

Intervention name: Placebo

Description: Sodium Chloride 0.9% Injection

Arm group label: Sodium Chloride (0.9%) for Injection

Other name: Sodium Chloride 0.9% Injection

Eligibility

Criteria:

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).

Gender: All

Minimum age: 16 Years

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Ross R Bullock, M.D., PhD Principal Investigator University of Miami, Lois Pope Life Center
Location
facility
Arrowhead Regional Medical Center | Colton, California, 92324, United States
University of California, Davis Medical Center | Sacramento, California, 95817, United States
The Queen's Medical Center | Honolulu, Hawaii, 96813, United States
Detroit Receiving Hospital and University Health Center | Detroit, Michigan, 48201, United States
Sinai Grace Hospital | Detroit, Michigan, 48235, United States
University of Pittsburgh Medical Center | Pittsburgh, Pennsylvania, 15213, United States
Location Countries

United States

Verification Date

February 2018

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: NNZ-2566

Arm group type: Experimental

Description: 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.

Arm group label: Sodium Chloride (0.9%) for Injection

Arm group type: Placebo Comparator

Description: 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.

Acronym INTREPID2566
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov