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

Shinkei Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Traumatic Brain Injury

Treatments: Drug: Placebo; Drug: Amantadine Hydrochloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT06253923

MR-301-T-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age: 18 to 65 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

45 participants in 2 patient groups, including a placebo group

MR-301

Active Comparator group

Description:

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

Treatment:

Drug: Amantadine Hydrochloride

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo