ASURE: Alzheimer Study Using oRal Edaravone

Sponsor

Treeway B.V. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05323812

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: TW001 Drug: Placebo	Phase 2

Detailed Description

This is an exploratory, double-blind, randomized, placebo-controlled phase IIa proof of concept study to evaluate the safety, pharmacodynamics and pharmacokinetics of TW001 in patients with mild AD. Patients will be randomized 1:1 to TW001 and placebo. Treatments will be given in a fasted state once daily for 90 days. The total duration of the clinical trial will be approximately 4 months per patient.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Pharmacodynamics and Pharmacokinetics of TW001 in Alzheimer Patients

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TW001	Drug: TW001 daily dose of 100 mg TW001/placebo Other Names: Edaravone
Placebo Comparator: Placebo	Drug: Placebo daily dose of 100 mg TW001/placebo

Arm

Intervention/Treatment

Experimental: TW001

Drug: TW001

daily dose of 100 mg TW001/placebo

Other Names:

Edaravone

Placebo Comparator: Placebo

Drug: Placebo

daily dose of 100 mg TW001/placebo

Outcome Measures

Primary Outcome Measures

Nature, frequency and severity of adverse events [Through study completion, up to 4 months]
Safety and tolerability as measured by nature, frequency and severity of adverse events and serious adverse events
Plasma oxidative stress biomarkers [Through study completion, up to 4 months]
Changes from baseline in: 8-OHdG/8-OHG and Uric acid in plasma
Cerebrospinal Fluid (CSF) oxidative stress biomarkers [Through study completion, up to 4 months]
Changes from baseline in: 8-OHdG/8-OHG in CSF

Secondary Outcome Measures

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 Outcome Measures

Plasma biomarkers of AD pathology and neurodegeneration [Through study completion, up to 4 months]
Changes from baseline in: Aβ42, Aβ40, phosphorylated tau epitopes, GFAP and NfL
CSF biomarkers of AD pathology and neurodegeneration [Through study completion, up to 4 months]
Changes from baseline in: Aβ42, Aβ40, phosphorylated tau epitopes, t-tau, GFAP, YKL-40, NfL and NRGN
Urine oxidative stress biomarkers [Through study completion, up to 4 months]
Changes from baseline in: 8-OHdG/8-OHG in urine
Cognitive assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB) [Through study completion, up to 4 months]
Change from baseline in CDR-SB score

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 55-80 years (both inclusive), male or female.
Body mass index between 18.5 to 30.0 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, the dose must be stable for at least the last 3 months before screening, and the patient must be willing to remain on the same 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:

Has reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone [FSH] levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea);
Is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or
Has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g., anorexia nervosa).
Capable of providing informed consent and complying with trial procedures.

Exclusion Criteria:

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.
Evidence of a clinically relevant or unstable psychiatric disorder, based on the 5th edition after text revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5TM) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium. Major depression in remission is not exclusionary.
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 3 years prior to screening, except adequately treated squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
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.
Use of Organic Anion Transporter (OAT)-3 inhibitors such as probenecid, cimetidine, and diclofenac.
Current substance or alcohol dependence.
Exposure to any investigational drug within 30 days of the screening visit.