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

NCT06253923 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MR-301-T-001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 13

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.

Conditions

Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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

Study Arms (2)

MR-301

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Amantadine Hydrochloride DRUG

MR-301 is an I.V. formulation for the treatment of TBI. The active ingredient is amantadine hydrochloride (HCl).

MR-301

Placebo DRUG

The placebo for this study is 0.9% Sodium Chloride IV Solution.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 to 75 years.
• Patients with TBI confirmed by CT scan or MRI
• Patient have sustained a trauma between 72 hours to 1 week
• Patient with Abbreviated Injury Score (AIS) ≤ 2.
• Patients must be admitted to an acute care setting no less than 2 days prior to randomization.
• Glasgow Coma Score of 3 to 8, inclusive.
• Patients must be unable to consistently follow commands or to engage in functional communication, as assessed by the score on the CRS-R.
• Patients have at least one reactive pupil.
• Must have a Legally Authorized Representative (LAR) able to provide consent for the trial.
• 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)\].

You may not qualify if:

• Life expectancy of less than 24 hours.
• Patient has any spinal cord injury.
• Patient has a penetrating head injury.
• Patient has bilaterally fixed dilated pupils
• 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.
• Patient has poorly controlled seizure more than one per month.
• Prior history of status epilepticus
• Prior treatment with or a sensitivity to amantadine HCl or amantadine.
• Patient has screening lab measurements outside the normal range
• Absolute neutrophil count (ANC): ≤ 1.5 x 109/L
• Hemoglobin ≤ 8 g/dL or active bleeding requiring ongoing transfusions.
• Platelets ≤ 80 x 109/L or active bleeding requiring ongoing transfusions.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) or total bilirubin (unless isolated Gilbert's syndrome) ≥ 2x the upper limit of normal (ULN)
• Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m2
• Patient has received treatment with an investigational drug, CNS stimulant or dopamine antagonist/agonist within 4 weeks.

Sponsors & Collaborators

• SHINKEI Therapeutics, Inc: lead
• Duke Clinical Research Institute: collaborator

Study Sites (13)

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

UF Health Heart and Vascular Hospital

Gainesville, Florida, 32608, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Hackensack Meridian Health Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

Location

University of New Mexico Hospital

Albuquerque, New Mexico, 87106, United States

Location

Department of Neurology, Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

McGovern Medical School, University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

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: February 2, 2024
• First Posted: February 12, 2024
• Study Start: June 1, 2024
• Primary Completion: July 31, 2025
• Study Completion: August 1, 2025
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)