ConcussionPhase 2NCT02100150
A Safety and Efficacy Study of NNZ-2566 in Patients With Mild Traumatic Brain Injury (mTBI)
A Phase 2 study testing NNZ-2566 in people with Concussion, run by Neuren Pharmaceuticals Limited at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 55 years
- Conditions the study is for
- Concussion
- What is being tested?
- NNZ-2566
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
- 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.
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- 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]).
Who cannot join
- Subjects are ineligible for the study if they meet any of the following exclusion criteria:
- 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 seizure disorder or has experienced seizures in the 24 hours preceding Screening. Note: Isolated febrile seizures during early childhood are not exclusionary.
- 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.
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- 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.
- Subject has an average QT interval corrected using Fridericia's formula (QTcF) >450 msec at Screening or any ECG abnormality that may pose a potential safety concern.
- Subject has a history of risk factors for torsade de pointes (e.g., heart failure, clinically significant hypokalemia, a serum potassium value at Screening of <3.0 mmol/L, or a family history of long QT syndrome).
- Subject has a history of QT/QTcF prolongation previously or currently controlled with medication, in which normal QT/QTcF intervals could or can only be achieved with medication.
- Subject has participated in another clinical treatment study within the 4 weeks preceding Screening.
- Subject is unable to provide informed consent (where deemed cognitively able by standard assessments) or informed consent cannot be obtained from a legally authorized individual (e.g., spouse, or in the instance of minors, a parent).
- Subject is pregnant or nursing.
- Subject was previously enrolled in this study.
- Subject has an allergy to strawberries.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of NNZ-2566 in the Acute Treatment of Adolescents and Adults With Mild Traumatic Brain Injury (mTBI)
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.
Read the detailed description
Traumatic brain injury (TBI) is an injury to the head caused by an external trauma that can lead to brain cell death, inflammation, edema, hemorrhage, and disruption of normal brain cell function. mTBI frequently results in persistent functional impairment including problems with cognitive function, memory, mood, and other personality disorders.
There are currently no drugs available to reduce the brain damage or sequelae that result from TBI. Clearly, a safe and effective treatment for concussion injury and all forms of TBI would be an important development for military personnel as well as the general population.
This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescents and adults with mTBI. The study also will also investigate measures of efficacy during treatment.
- Conditions
- Concussion
- Being tested
- NNZ-2566, Placebo
- Keywords
- Concussion
- Medical subject headings
- Brain Concussion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NNZ-2566Drug
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.
PlaceboDrug
Also called Strawberry flavored solution
Strawberry flavored solution 0.5% v/v in Water for Injection
| Study group | Role | What they receive |
|---|---|---|
| NNZ-2566 | Experimental | Glycyl-L-2-Methylpropyl-L-Glutamic Acid Receives: Drug: NNZ-2566 |
| Placebo (strawberry flavored solution) | Placebo comparator | Strawberry flavored solution and water Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Day 28
Secondary outcomes (3)
Safety
Incidence of adverse events (AE), including Serious adverse events (SAE), will be evaluated between the two NNZ-2566 doses and placebo. Incidence of AEs and SAEs will be evaluated from randomized dosing through to Day 28 or the final study visit, whichever comes later.
Measured: Screening through to Day 28 or the final study visit, whichever comes later
Pharmacodynamic Measurements of Protein Biomarkers and micro-RNA
A blood sample will be obtained to measure levels of protein biomarkers (SBDP150, S100, GFAP, and UCH-L1) that are derived from the cytosol of neurons, astrocytes, axons; micro-RNA (mi-RNA) levels will also be measured. This blood sample will be obtained at Screening, and on Days 1, 2, and 3.
Measured: 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
The following pharmacokinetic measures will be calculated from NNZ-2566 concentrations in whole blood: Cmax, Cmin, and AUC at steady-state.
A PK blood sample (2 x 2 mL) will be collected on Day 3 at approximately 2 to 4 hours after administration of study drug, and on Day 7 at pre-dose and approximately 4 hours after administration of study drug.
Measured: Day 3 and Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ConcussionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuren Pharmaceuticals Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wesley R Cole, Ph.D, Principal investigator, Fort BraggKurt Denninghoff, MD, Principal investigator, University of ArizonaAlex Hishaw, MD, Principal investigator, University of ArizonaBrian O'Neil, MD, Principal investigator, Detroit Receiving Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100150
- Sponsor's protocol ID
- Neu-2566-TBI-003
- Status last verified
- Feb 2018
- First submitted
- 19 Mar 2014
- Last updated
- 5 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of NNZ-2566 in the Acute Treatment of Adolescents and Adults With Mild Traumatic Brain Injury (mTBI)
- ClinicalTrials.gov ID
- NCT02100150
- Acronym / sponsor ID
- Neu-2566-TBI-003
- Conditions
- Concussion
- Keywords
- Concussion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Neuren Pharmaceuticals LimitedIndustry (pharma, biotech, devices)
- Study start
- Sep 2014 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 31 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Traumatic brain injury (TBI) is an injury to the head caused by an external trauma that can lead to brain cell death, inflammation, edema, hemorrhage, and disruption of normal brain cell function. mTBI frequently results in persistent functional impairment including problems with cognitive function, memory, mood, and other personality disorders.
There are currently no drugs available to reduce the brain damage or sequelae that result from TBI. Clearly, a safe and effective treatment for concussion injury and all forms of TBI would be an important development for military personnel as well as the general population.
This study will investigate the safety and tolerability of treatment with oral administration of NNZ-2566 at 35 mg/kg or 70 mg/kg BID in adolescents and adults with mTBI. The study also will also investigate measures of efficacy during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NNZ-2566 | Experimental | Drug: NNZ-2566Glycyl-L-2-Methylpropyl-L-Glutamic Acid |
| Placebo (strawberry flavored solution) | Placebo comparator | Drug: PlaceboStrawberry flavored solution and water |
Who may qualify
- Ages
- 16 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Subject has a diagnosis of mTBI resulting from an injury that meets the following criteria:
- 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.
Key exclusion criteria (25 listed)
- Subjects are ineligible for the study if they meet any of the following exclusion criteria:
- 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 seizure disorder or has experienced seizures in the 24 hours preceding Screening. Note: Isolated febrile seizures during early childhood are not exclusionary.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NNZ-2566Glycyl-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. | Drug | NNZ-2566 |
| PlaceboAlso: Strawberry flavored solutionStrawberry flavored solution 0.5% v/v in Water for Injection | Drug | Placebo (strawberry flavored solution) |
Primary outcome
Cognitive Function - Automated Neuropsychological Assessment Metrics (ANAM)
Time frame: Through to Day 28
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.
General Clinical Status - Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I)
Time frame: Through to Day 28
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.
Post-Injury Symptoms
Time frame: Through to Day 28
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.
Postural Stability
Time frame: Through to Day 28.
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.
Psychological Sequelae
Time frame: Through to Day 28
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).
Change in subject's readiness and fitness to return to work as measured by the Return-to-Duty Assessment
Time frame: Day 3 to 28
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.
Residual Functional Disability
Time frame: Day 28
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.
3 secondary outcomes
Safety
Time frame: Screening through to Day 28 or the final study visit, whichever comes later
Pharmacodynamic Measurements of Protein Biomarkers and micro-RNA
Time frame: 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
Time frame: Day 3 and Day 7
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wesley R Cole, Ph.D principal investigator
Fort Bragg
Kurt Denninghoff, MD principal investigator
University of Arizona
Alex Hishaw, MD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NNZ-2566 in people with Concussion, run by Neuren Pharmaceuticals Limited at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function - Automated Neuropsychological Assessment Metrics (ANAM) (time frame: Through to Day 28). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2018.