ASURE: Alzheimer Study Using oRal Edaravone

NCT05323812 | Completed Phase 2

• 2 other identifiers: TW001-AD-C2.012021-003164-27
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 6

Brief Summary

This is a multi-center, Phase IIa, randomized, double-blind, placebo-controlled study in patients with Alzheimer's Disease (AD).

Conditions

Alzheimer Disease

Keywords

Alzheimer's Disease; Oxidative stress biomarkers; Free radical scavenger; Edaravone

Outcome Measures

Primary Outcomes (3)

• Nature, frequency and severity of adverse events

  Safety and tolerability as measured by nature, frequency and severity of adverse events and serious adverse events

  Through study completion, up to 4 months

• Plasma oxidative stress biomarkers

  Changes from baseline in: 8-OHdG/8-OHG and Uric acid in plasma

  Through study completion, up to 4 months

• Cerebrospinal Fluid (CSF) oxidative stress biomarkers

  Changes from baseline in: 8-OHdG/8-OHG in CSF

  Through study completion, up to 4 months

Secondary Outcomes (4)

• Plasma concentration of TW001

  Through study completion, up to 4 months

• Area under the concentration versus time curve (AUC) of TW001

  Through study completion, up to 4 months

• Maximum plasma concentration (Cmax) of TW001

  Through study completion, up to 4 months

• Time to reach maximum plasma concentration (tmax) of TW001

  Through study completion, up to 4 months

Other Outcomes (4)

• Plasma biomarkers of AD pathology and neurodegeneration

  Through study completion, up to 4 months

• CSF biomarkers of AD pathology and neurodegeneration

  Through study completion, up to 4 months

• Urine oxidative stress biomarkers

  Through study completion, up to 4 months

Study Arms (2)

TW001

EXPERIMENTAL

Drug: TW001

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TW001 DRUG

daily dose of 100 mg TW001/placebo

Also known as: Edaravone

TW001

Placebo DRUG

daily dose of 100 mg TW001/placebo

Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-80 years (both inclusive), male or female.
• Body mass index between 18.5 to 33.0 kg/m2 (both inclusive).
• Should meet the criteria for early clinical stage Alzheimer's Disease (AD) according to the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria research framework:
• Gradual and progressive change in memory function reported by patient or informant over more than 6 months,
• Clinical syndrome of Mild Cognitive Impairment (MCI) due to AD or mild AD dementia,
• An Mini-Mental State Exam (MMSE) score ≥ 20 at screening,
• Biomarker classification according to the Amyloid/Tau/Neurodegeneration (ATN) as A+T+N+ or A+T+N- based upon:
• (i) Cerebrospinal fluid (CSF) profile consistent with AD (an Aβ42 concentration of \<1000 pg/mL AND phosphorylated tau (p-tau) \>19 pg/mL, or a ratio of p-tau/Aβ42 of ≥0.020) taken during the screening period prior to the day of the first dose of study medication, or
• (ii) Documented evidence of a CSF profile consistent with AD obtained with the previous 12 months, or
• (iii) Documented amyloid positron emission tomography (PET) scan evidence acquired within the previous 12 months.
• A reliable and competent trial partner/caregiver who can assist and witness dosing and is willing to accompany the patient to all visits. The trial partner/caregiver should understand the nature of the trial and adhere to trial requirements (e.g., visit schedules, evaluations) and confirm this by co-signing the informed consent of the patient or signing of a separate informed consent of the partner/caregiver according to the local requirements.
• If a patient is taking medication, supplements or vitamins that may have an influence on oxidative stress, cognition and/or EEG, the dose must be stable at screening for at least one month, and the patient must be willing to remain on the same treatment and dose for the duration of the trial.
• A male patient abstains from sexual intercourse, or is vasectomized (\> 6 months), or will use a condom with spermicide during sexual intercourse during the trial and for three months after participation in the trial and will abstain from sperm donation during the trial and for three months after participation in the trial.
• A female patient should not be of reproductive potential:
• A female patient who is not of reproductive potential is defined as one who:

You may not qualify if:

• A known history of stroke that is clinically important in the investigator's opinion.
• Evidence of a clinically relevant neurological disorder other than AD at screening, including but not limited to: vascular dementia, Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, dementia with Lewy bodies, other types of dementia, neurosyphilis or head trauma with loss of consciousness that led to persistent cognitive deficits.
• A history of seizures or epilepsy within the last 5 years before screening.
• Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation.
• Patient has a history of any of the following conditions:
• Clinically significant hepatic disease,
• AST or ALT levels of ≥ 2 times upper limit of normal (ULN),
• Biliary tract disease,
• Patient has a positive screening test for HIV, hepatitis B or C.
• Presence of any of the following clinical conditions:
• Unstable cardiac, pulmonary, endocrine, hematologic or active infectious disease,
• Unstable psychiatric illness defined as psychosis, untreated major depression within 90 days of the screening visit,
• A history of cancer within the past 3 years prior to screening other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in situ, or in-situ prostate cancer or in-situ breast cancer which have been fully removed and are considered cured
• History or signs/symptoms of lumbar spine/disc disease including but not limited to scoliosis, herniation, or any other contraindication to lumbar puncture.
• History of known sensitivity or intolerability to edaravone, related substances of edaravone, or to any of the excipients.

Sponsors & Collaborators

• Treeway B.V.: lead

Study Sites (6)

University Hospital Centre Osijek

Osijek, 31000, Croatia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Brain Research Center Den Bosch

's-Hertogenbosch, 5223 LA, Netherlands

Location

Brain Research Center Amsterdam

Amsterdam, 1081 GN, Netherlands

Location

ETZ Elisabeth ziekenhuis

Tilburg, 5022 GC, Netherlands

Location

Brain Research Center Zwolle

Zwolle, 8025 AZ, Netherlands

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Edaravone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Antipyrine; Pyrazolones; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2022
• First Posted: April 12, 2022
• Study Start: March 1, 2023
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: April 23, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4); CR (2)