Clinical trial NCT06253923: Study to Assess the Safety of Amantadine Hydrochloride (HCl) Intravenous (IV) Solution (MR-301) in Patients With Severe Traumatic Brain Injury (TBI).
Official title: Multicenter, Double-blind, Randomized, Placebo Controlled, Study to Assess the Safety of Amantadine Hydrochloride (HCl) Intravenous (IV) Solution (MR-301), in Patients With Severe Traumatic Brain Injury (TBI).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Traumatic Brain Injury
Lead sponsor: SHINKEI Therapeutics, Inc
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
First posted: 2024-02-12
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main goal of this clinical trial is to check if the treatment is safe and well-tolerated. Researchers will compare the MR-301 active drug group with the placebo group to evaluate the safety and tolerability of the drug. Other measurements include assessing the patient's overall outcome, neurological responses, time spent in the intensive care unit, time in the hospital, and mortality. Participants will receive either MR-301 BID IV dosing or a matching placebo for a total of 3 weeks.

Detailed description: This is a multi-center, randomized, placebo-controlled study of MR-301 administered BID IV in patients with severe TBI.

Participant: 45 patients with severe TBI who maintain GCS scores 3-8 both inclusive.

Intervention: Mr-301 or placebo will be administered intravenously BID for upto 3 weeks.

Primary Outcome: Safety and Tolerability of MR-301

Secondary Outcome: GOS-E, CRS-R, DRS, FOUR score, time to ICU discharge, time to hospital discharge and mortality.

Eligibility criteria: Inclusion Criteria:

1. Age: 18 to 75 years.
2. Patients with TBI confirmed by CT scan or MRI
3. Patient have sustained a trauma between 72 hours to 1 week
4. Patient with Abbreviated Injury Score (AIS) ≤ 2.
5. Patients must be admitted to an acute care setting no less than 2 days prior to randomization.
6. Glasgow Coma Score of 3 to 8, inclusive.
7. Patients must be unable to consistently follow commands or to engage in functional communication, as assessed by the score on the CRS-R.
8. Patients have at least one reactive pupil.
9. Must have a Legally Authorized Representative (LAR) able to provide consent for the trial.
10. Patient must have stable vitals ---Intracranial pressure ICP Value is at discretion of investigator), systolic blood pressure (SBP\>90 mmHg) partial pressure of oxygen (PaO2 \> 60 mmHg)\].

Exclusion Criteria:

1. Life expectancy of less than 24 hours.
2. Patient has any spinal cord injury.
3. Patient has a penetrating head injury.
4. Patient has bilaterally fixed dilated pupils
5. Patients with history of any medical or psychiatric disorder, or any severe concomitant disease that would, in the opinion of the Investigator, interfere with clinical assessment.
6. Patient has poorly controlled seizure more than one per month.
7. Prior history of status epilepticus
8. Prior treatment with or a sensitivity to amantadine HCl or amantadine.
9. Patient has screening lab measurements outside the normal range

   1. Absolute neutrophil count (ANC): ≤ 1.5 x 109/L
   2. Hemoglobin ≤ 8 g/dL or active bleeding requiring ongoing transfusions.
   3. Platelets ≤ 80 x 109/L or active bleeding requiring ongoing transfusions.
   4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) or total bilirubin (unless isolated Gilbert's syndrome) ≥ 2x the upper limit of normal (ULN)
   5. Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2
10. Patient has received treatment with an investigational drug, CNS stimulant or dopamine antagonist/agonist within 4 weeks.
11. Patient has a history of NYHA Class 3 or Class 4 Congestive Heart Failure within the last 5 years.
12. Females who are nursing, pregnant, or planning to become pregnant
13. any other clinically significant medical condition as determined by the Investigator, that may unfavorably alter the risk benefit of study participation.
14. Patient has prolonged QT interval.
15. Treatment with a systemic anticholinergic medication within 1 week prior to screening.

Primary outcomes:
measure: Frequency, severity, and type of adverse events and serious adverse events between active treatment and placebo groups
timeFrame: Day 1 to Day 35
Secondary outcomes:
measure: Change from baseline in Glasgow Outcome Scale-Extended
timeFrame: Day 21 and Day 35
measure: Change from baseline in Disability Rating Scale (DRS) scale
timeFrame: Day 5, Day 10, Day 15, Day 21
measure: Change from baseline in Coma Recovery Scale - Revised
timeFrame: Day 5, Day 10, Day 15, Day 21
measure: Change from baseline in Full Outline of UnResponsiveness (FOUR) score
timeFrame: every day up to Day 21
measure: Time to intensive care unit (ICU) discharge to hospital floor
timeFrame: up to day 21
measure: Time to hospital discharge from randomization
timeFrame: up to day 21
measure: Mortality assessment at end of treatment period
timeFrame: Day 21
measure: Mortality assessment at end of study period (Day 35).
timeFrame: Day 35
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles General Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Gainesville
country: United States
facility: UF Health Heart and Vascular Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Barnes Jewish Hospital
state: Missouri
city: Albuquerque
country: United States
facility: University of New Mexico Hospital
state: New Mexico
city: Durham
country: United States
facility: Department of Neurology, Duke University School of Medicine
state: North Carolina
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: McGovern Medical School, University of Texas Health Science Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: