Assessing the safety of intravenous Amantadine for severe traumatic brain injury

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).

This study is testing if giving Amantadine through an IV is safe for people with severe traumatic brain injuries compared to a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: SHINKEI Therapeutics, Inc (Industry-sponsored)
• Locations: 12 sites (Los Angeles, California and 11 other locations)
• Trial ID: NCT06253923 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and tolerability of Amantadine Hydrochloride (MR-301) administered intravenously in patients with severe traumatic brain injury (TBI). It is a multi-center, randomized, placebo-controlled study where participants will receive either the active drug or a placebo for up to three weeks. The study will measure various outcomes, including neurological responses, time spent in the intensive care unit, and overall patient outcomes. The primary focus is on assessing the safety of the treatment compared to a placebo.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with severe TBI and a Glasgow Coma Score between 3 and 8.

Not a fit: Patients with life expectancy of less than 24 hours or those with penetrating head injuries will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve recovery outcomes for patients with severe traumatic brain injury.

How similar studies have performed: Other studies have shown promise in using Amantadine for TBI, but this specific approach is still being evaluated.

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.

Where this trial is running

Los Angeles, California and 11 other locations

• Los Angeles General Medical Center — Los Angeles, California, United States (Recruiting)
• UC Davis Medical Center — Sacramento, California, United States (Recruiting)
• UF Health Heart and Vascular Hospital — Gainesville, Florida, United States (Recruiting)
• Tampa General Hospital — Tampa, Florida, United States (Recruiting)
• Maine Medical Center — Portland, Maine, United States (Recruiting)
• Wayne State University — Detroit, Michigan, United States (Recruiting)
• Barnes Jewish Hospital — Saint Louis, Missouri, United States (Recruiting)
• University of New Mexico Hospital — Albuquerque, New Mexico, United States (Recruiting)
• Department of Neurology, Duke University School of Medicine — Durham, North Carolina, United States (Recruiting)
• Penn Presbyterian Medical Center — Philadelphia, Pennsylvania, United States (Recruiting)
• McGovern Medical School, University of Texas Health Science Center — Houston, Texas, United States (Recruiting)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (Recruiting)

Study contacts

• Study coordinator: Adhiraj Dharmadhikari

Conditions Traumatic Brain Injury