A Safety and Efficacy Study of NNZ-2566 in Patients With Mild Traumatic Brain Injury (mTBI)

NCT02100150 | Terminated Phase 2 DMC

• 1 other identifier: Neu-2566-TBI-003
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether NNZ-2566 is safe and well tolerated in the treatment of mTBI in adolescents and adults.

Conditions

Concussion

Keywords

Concussion

Outcome Measures

Primary Outcomes (7)

• Cognitive Function - Automated Neuropsychological Assessment Metrics (ANAM)

  The ANAM is a library of computerized tests that measures 6 cognitive domains believed to be most highly impacted by mTBI: simple reaction time, procedural reaction time, learning, working memory, delayed memory, and spatial memory. Only selected subtests of the ANAM will be performed during this study, as follows: * Code substitution - learning, simple reaction time, procedural reaction time, code substitution. * Simple reaction time and procedural reaction time.

  Through to Day 28

• General Clinical Status - Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I)

  The CGI-S is an assessment that requires the clinician to rate the severity of the subject's illness at the time of assessment, relative to the clinician's past experience with subjects who have the same diagnosis.

  Through to Day 28

• Post-Injury Symptoms

  Residual self-reported symptoms associated with mTBI will be assessed using the Post-Concussion Symptom Scale (PCSS). The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is used to measure the presence and severity of post-concussion syndrome, which addresses a set of somatic, cognitive, and emotional symptoms following TBI.

  Through to Day 28

• Postural Stability

  Postural sway will be analysed using the Sway Balance Application. Sway Balance will be measured using the Balance Error Scoring System (BESS). Pupil size and dynamics as well as the associated neurological pupillary index (NPi) will be measured using a handheld, infrared, digital pupillometer. An Accommodation/Convergence test will be performed. Convergence is the inward rotational ability of the eye. Accommodation is the ability of the eye to maintain focus as the distance changes.

  Through to Day 28.

• Psychological Sequelae

  Anxiety and depression will be measured using the Hospital Anxiety and Depression Scale (HADS). Post-traumatic stress disorder will be measured by the Post-Traumatic Stress Disorder Checklist-Specific (PCL-S).

  Through to Day 28

• Change in subject's readiness and fitness to return to work as measured by the Return-to-Duty Assessment

  The Return-to-Duty Assessment is a standardized protocol to determine a subject's readiness or fitness to return to duty (yes/no). Once the subject has been cleared to return to duty, this assessment is no longer applicable for that subject.

  Day 3 to 28

• Residual Functional Disability

  Residual Functional Ability will be measured by the Sheehan Disability Scale (SDS) which measures the extent to which 3 major sectors in the subject's life are impaired by an illness or disorder.

  Day 28

Secondary Outcomes (3)

• Safety

  Screening through to Day 28 or the final study visit, whichever comes later

• Pharmacodynamic Measurements of Protein Biomarkers and micro-RNA

  Screening through to Day 3

• Pharmacokinetic (PK) Measurements - maximum observed concentration (Cmax), trough concentration (Cmin),and area under the concentration-time curve (AUC) at steady-state

  Day 3 and Day 7

Study Arms (2)

NNZ-2566

EXPERIMENTAL

Glycyl-L-2-Methylpropyl-L-Glutamic Acid

Drug: NNZ-2566

Placebo (strawberry flavored solution)

PLACEBO COMPARATOR

Strawberry flavored solution and water

Drug: Placebo

Interventions

NNZ-2566 DRUG

Glycyl-L-2-Methylpropyl-L-Glutamic Acid (NNZ-2566) supplied as a lyophilized powder (3g in 30 milliliter vials) for reconstitution with strawberry flavored solution 0.5% v/v in Water for Injection.

NNZ-2566

Placebo DRUG

Strawberry flavored solution 0.5% v/v in Water for Injection

Also known as: Strawberry flavored solution

Placebo (strawberry flavored solution)

Eligibility Criteria

• Age: 16 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject has a diagnosis of mTBI resulting from an injury that meets the following criteria:
• Occurred within 24 hours of Screening and was associated with a clear mechanism of injury and an alteration of consciousness (e.g., confusion, feeling dazed, or "seeing stars")
• Was associated with a GCS score of 13-15
• Was associated with 1 or more of the following signs and symptoms, as determined by a qualified clinician:
• i. Headache ii. Loss of consciousness iii. Post traumatic amnesia iv. Retrograde amnesia v. Difficulty concentrating vi. Balance problems vii. Dizziness viii. Visual problems ix. Personality changes x. Fatigue xi. Sensitivity to light/noise xii. Numbness xiii. Nausea xiv. Vomiting d. Current symptoms associated with the mTBI are causing clinically significant impairment
• Subject is 16 to 55 years old.
• Subject has a CGI-S score of ≥3 at Screening
• Subject has an RPQ-3 score of ≥3 at Screening
• Subjects who are taking psychotropic medications must have been receiving a stable regimen (i.e., same dosage and regimen) for at least 4 weeks prior to Screening. For the purposes of this protocol, psychotropic medications are defined as medications that are prescribed for intended CNS benefits. Medications for headache are permissible, as needed, according to approved prescribing information.
• Women of child-bearing potential must have a negative urine pregnancy test at Screening. Men and women must agree to use a contraceptive method with \<1% success rate (e.g., oral contraceptive, injectable progestogen, levonorgestrel implant, estrogenic vaginal ring, percutaneous contraceptive patch, intrauterine device \[IUD\], surgical sterilization, or double barrier method \[i.e., condom with diaphragm or spermicidal agent\]).

You may not qualify if:

• Subject has a history of brain surgery or prior severe TBI (based on a previously documented GCS score of ≤8).
• Subject has a history of diabetes mellitus requiring pharmacotherapy within the preceding 12 months.
• Subject has a history of hypothyroidism within the 3 years preceding Screening that currently requires or did require pharmacotherapy.
• Subject has regularly used more than 1 of the following psychoactive medications in the 4 weeks preceding Screening: methylphenidate, dextroamphetamine, mixed amphetamine salts, amantadine, memantine, cholinesterase inhibitors, modafinil, or armodafinil.
• Subject has a history of substance abuse or dependence, other than nicotine dependence, within the 3 months preceding Screening.
• Subject has signs/symptoms of acute impairment due to alcohol use.
• Subject has used anti-epileptic medications in the 4 weeks preceding Screening.
• Subject has used bromocryptine, levodopa, ropinirole, or pramipexole in the 4 weeks preceding Screening.
• Subject has a history of a major psychiatric disorder (including major depression, a clinically significant anxiety disorder, or a psychotic disorder) that is associated with significant clinical impairment within the preceding 6 months.
• In the Investigator's opinion, the subject poses a current homicidal or serious suicidal risk, and/or has made a suicide attempt within the 6 months preceding Screening.
• Subject has a neurological disorder other than mTBI (e.g., Parkinson's disease, stroke, multiple sclerosis, dementia, delirium, infectious encephalopathy) that has required treatment within the 6 months preceding Screening.
• Subject has a history of, or current, cerebrovascular disease.
• Subject has a history of, or current, malignancy.
• Subject has an unstable medical disorder that may pose a safety concern or interfere with the accurate assessment of safety or efficacy.
• Subject has laboratory values at Screening deemed to be clinically significant by the Investigator.

Sponsors & Collaborators

• Neuren Pharmaceuticals Limited: lead

Study Sites (1)

Fort Bragg

Fayetteville, North Carolina, 28307, United States

Location

MeSH Terms

Conditions

Brain Concussion

Interventions

trofinetide

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Study Officials

• Wesley R Cole, Ph.D

  Fort Bragg

  PRINCIPAL INVESTIGATOR

• Kurt Denninghoff, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Alex Hishaw, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Brian O'Neil, MD

  Detroit Receiving Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2014
• First Posted: March 31, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: February 5, 2018

Record last verified: 2018-02

Locations

US (1)