Study to Assess the Safety of Amantadine Hydrochloride (HCl) Intravenous (IV) Solution (MR-301) in Patients With Severe Traumatic Brain Injury (TBI).

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).

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Drug: Amantadine Hydrochloride; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health Heart and Vascular Hospital
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Barnes Jewish Hospital
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Hackensack Meridian Health Jersey Shore University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Department of Neurology, Duke University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • McGovern Medical School, University of Texas Health Science Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The placebo for this study is 0.9% Sodium Chloride IV Solution.
Active Comparator: MR-301; On first day, patient will receive MR-301 at 100 mg intravenous infusion BID. On second day, the dose is elevated to 150 mg intravenous infusion BID. On third day, the dose is further elevated to 200 mg intravenous infusion BID and maintained up to Day 21	Drug: Amantadine Hydrochloride; MR-301 is an I.V. formulation for the treatment of TBI. The active ingredient is amantadine hydrochloride (HCl).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency, severity, and type of adverse events and serious adverse events between active treatment and placebo groups	Safety and tolerability will be compared between active treatment and placebo groups.	Day 1 to Day 35

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Glasgow Outcome Scale-Extended	Day 21 and Day 35
Change from baseline in Disability Rating Scale (DRS) scale	Day 5, Day 10, Day 15, Day 21
Change from baseline in Coma Recovery Scale - Revised	Day 5, Day 10, Day 15, Day 21
Change from baseline in Full Outline of UnResponsiveness (FOUR) score	every day up to Day 21
Time to intensive care unit (ICU) discharge to hospital floor	up to day 21
Time to hospital discharge from randomization	up to day 21
Mortality assessment at end of treatment period	Day 21
Mortality assessment at end of study period (Day 35).	Day 35

Collaborators and Investigators

• Sponsor: SHINKEI Therapeutics, Inc
• Collaborators: Duke Clinical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries, Traumatic; Wounds and Injuries; Brain Injuries; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Antiviral Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Amantadine
• Other Study ID Numbers: MR-301-T-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No