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Study of NNZ-2566 in Patients With Traumatic Brain Injury Under EFIC (INTREPID2566)

Primary Purpose

Brain Injuries

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

NNZ-2566

Placebo

About this trial

This is an interventional treatment trial for Brain Injuries

Eligibility Criteria

16 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Arrowhead Regional Medical Center
University of California, Davis Medical Center
The Queen's Medical Center
Detroit Receiving Hospital and University Health Center
Sinai Grace Hospital
University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

NNZ-2566

Sodium Chloride (0.9%) for Injection

Arm 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.

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.

Outcomes

Primary Outcome Measures

Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

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))

Improvement in cognitive and neuropsychological functioning.

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.

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.

Full Information

NCT ID

NCT01366820

First Posted

May 29, 2011

Last Updated

February 1, 2018

Sponsor

Neuren Pharmaceuticals Limited

1. Study Identification

Unique Protocol Identification Number

NCT01366820

Brief Title

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

Acronym

INTREPID2566

Official Title

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 Type

Interventional

2. Study Status

Record Verification Date

February 2018

Overall Recruitment Status

Completed

Study Start Date

February 2013 (undefined)

Primary Completion Date

January 2016 (Actual)

Study Completion Date

January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Neuren Pharmaceuticals Limited

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Injuries

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

261 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NNZ-2566

Arm Type

Experimental

Arm Description

Arm Title

Sodium Chloride (0.9%) for Injection

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

NNZ-2566

Other Intervention Name(s)

Glycyl-L-2-Methylprolyl-L-Glutamic Acid

Intervention 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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sodium Chloride 0.9% Injection

Intervention Description

Sodium Chloride 0.9% Injection

Primary Outcome Measure Information:

Title

Reduced incidence, compared to placebo, of adverse events (AEs) and serious adverse events (SAEs)

Time Frame

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 Information:

Title

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))

Time Frame

1 month (defined as 4-6 weeks) and 3 months (defined as 12-14 weeks), post randomization.

Title

Improvement in cognitive and neuropsychological functioning.

Time Frame

1 month (defined as 4-6 weeks) and at 3 months (defined as 12-14 weeks), post randomization.

Title

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.

Time Frame

Baseline through to 72 hours post-start of infusion.

Title

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.

Time Frame

Start of infusion through to 12 hours post infusion.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ross R Bullock, M.D., PhD

Organizational Affiliation

University of Miami, Lois Pope Life Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Arrowhead Regional Medical Center

City

Colton

State/Province

California

ZIP/Postal Code

92324

Country

United States

Facility Name

University of California, Davis Medical Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

Facility Name

The Queen's Medical Center

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96813

Country

United States

Facility Name

Detroit Receiving Hospital and University Health Center

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Sinai Grace Hospital

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48235

Country

United States

Facility Name

University of Pittsburgh Medical Center

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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