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

Traumatic Brain Injury Clinical Trial

Official title:

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).

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06253923
• Other study ID #: MR-301-T-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 28, 2024
• Est. completion date: August 2024

Study information

• Verified date: February 2024
• Source: SHINKEI Therapeutics, Inc
• Contact: Adhiraj Dharmadhikari
• Phone: 1 (609) 423-1570
• Email: dharmadhikaria[@]shinkeitherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: August 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Drug:
• Amantadine Hydrochloride
MR-301 is an I.V. formulation for the treatment of TBI. The active ingredient is amantadine hydrochloride (HCl).
• Placebo
The placebo for this study is 0.9% Sodium Chloride IV Solution.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
SHINKEI Therapeutics, Inc	Duke Clinical Research Institute

Outcome

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