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

Phase 2

Recruiting

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Placebo; Drug: Amantadine Hydrochloride

• Registration Number: NCT06253923
• Lead Sponsor: SHINKEI Therapeutics, Inc

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.

Study Timeline

• Study First Submitted: 2024-02-02
• Study First Submitted QC: 2024-02-09
• Study First Posted: 2024-02-12
• Study Start: 2024-06-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-10-24
• Primary Completion: 2025-03
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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)].

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
MR-301	Amantadine Hydrochloride	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Disability Rating Scale (DRS) scale	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
Mortality assessment at end of study period (Day 35).	Day 35
Change from baseline in Coma Recovery Scale - Revised	Day 5, Day 10, Day 15, Day 21
Change from baseline in Glasgow Outcome Scale-Extended	Day 21 and Day 35
Time to hospital discharge from randomization	up to day 21
Mortality assessment at end of treatment period	Day 21

Trial Locations

Locations (11)

UC Davis Medical Center; 🇺🇸 Sacramento, California, United States

Tampa General Hospital; 🇺🇸 Tampa, Florida, United States

UF Health Heart and Vascular Hospital; 🇺🇸 Gainesville, Florida, United States

Maine Medical Center; 🇺🇸 Portland, Maine, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Penn Presbyterian Medical Center; 🇺🇸 Philadelphia, Pennsylvania, United States

McGovern Medical School, University of Texas Health Science Center; 🇺🇸 Houston, Texas, United States

Los Angeles General Medical Center; 🇺🇸 Los Angeles, California, United States

Barnes Jewish Hospital; 🇺🇸 Saint Louis, Missouri, United States

University of New Mexico Hospital; 🇺🇸 Albuquerque, New Mexico, United States

Department of Neurology, Duke University School of Medicine; 🇺🇸 Durham, North Carolina, United States