ASURE: Alzheimer Study Using oRal Edaravone

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05323812
• Other study ID #: TW001-AD-C2.01
• Secondary ID: 2021-003164-27
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2023
• Est. completion date: June 2024

Study information

• Verified date: January 2024
• Source: Treeway B.V.
• Contact: Frank Ruwe
• Phone: +31625375343
• Email: frank[@]treeway.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age 55-80 years (both inclusive), male or female.

2. Body mass index between 18.5 to 33.0 kg/m2 (both inclusive).

3. 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:

1. Gradual and progressive change in memory function reported by patient or informant over more than 6 months,

2. Clinical syndrome of Mild Cognitive Impairment (MCI) due to AD or mild AD dementia,

3. An Mini-Mental State Exam (MMSE) score = 20 at screening,

4. 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 Aß42 concentration of <1000 pg/mL AND phosphorylated tau (p-tau) >19 pg/mL, or a ratio of p-tau/Aß42 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.

4. 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.

5. 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.

6. 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.

7. A female patient should not be of reproductive potential:

A female patient who is not of reproductive potential is defined as one who:

1. 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);

2. Is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy; or

3. 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).

8. Capable of providing informed consent and complying with trial procedures.

Exclusion Criteria:

1. A known history of stroke that is clinically important in the investigator's opinion.

2. 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.

3. A history of seizures or epilepsy within the last 5 years before screening.

4. 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.

5. Renal impairment as indicated by a creatinine clearance of less than 50 mL/min as calculated by the Cockcroft Gault equation.

6. Patient has a history of any of the following conditions:

1. Clinically significant hepatic disease,

2. AST or ALT levels of = 2 times upper limit of normal (ULN),

3. Biliary tract disease,

4. Patient has a positive screening test for HIV, hepatitis B or C.

7. Presence of any of the following clinical conditions:

1. Unstable cardiac, pulmonary, endocrine, hematologic or active infectious disease,

2. Unstable psychiatric illness defined as psychosis, untreated major depression within 90 days of the screening visit,

3. 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

8. History or signs/symptoms of lumbar spine/disc disease including but not limited to scoliosis, herniation, or any other contraindication to lumbar puncture.

9. History of known sensitivity or intolerability to edaravone, related substances of edaravone, or to any of the excipients.

10. Current substance or alcohol dependence.

11. Exposure to any investigational drug within 30 days of the screening visit.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• TW001
daily dose of 100 mg TW001/placebo
• Placebo
daily dose of 100 mg TW001/placebo

Locations

Country	Name	City	State
Croatia	University Hospital Centre Osijek	Osijek
Croatia	University Hospital Centre Zagreb	Zagreb
Netherlands	Brain Research Center Amsterdam	Amsterdam
Netherlands	Brain Research Center Den Bosch	Den Bosch
Netherlands	ETZ Elisabeth ziekenhuis	Tilburg
Netherlands	Brain Research Center Zwolle	Zwolle

Sponsors (1)

Lead Sponsor	Collaborator
Treeway B.V.

Countries where clinical trial is conducted

Croatia,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma biomarkers of AD pathology and neurodegeneration	Changes from baseline in: Aß42, Aß40, phosphorylated tau epitopes, GFAP and NfL	Through study completion, up to 4 months
Other	CSF biomarkers of AD pathology and neurodegeneration	Changes from baseline in: Aß42, Aß40, phosphorylated tau epitopes, t-tau, GFAP, YKL-40, NfL and NRGN	Through study completion, up to 4 months
Other	Urine oxidative stress biomarkers	Changes from baseline in: 8-OHdG/8-OHG in urine	Through study completion, up to 4 months
Other	Cognitive assessment - Clinical Dementia Rating - Sum of Boxes (CDR-SB)	Change from baseline in CDR-SB score	Through study completion, up to 4 months
Primary	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
Primary	Plasma oxidative stress biomarkers	Changes from baseline in: 8-OHdG/8-OHG and Uric acid in plasma	Through study completion, up to 4 months
Primary	Cerebrospinal Fluid (CSF) oxidative stress biomarkers	Changes from baseline in: 8-OHdG/8-OHG in CSF	Through study completion, up to 4 months
Secondary	Plasma concentration of TW001		Through study completion, up to 4 months
Secondary	Area under the concentration versus time curve (AUC) of TW001		Through study completion, up to 4 months
Secondary	Maximum plasma concentration (Cmax) of TW001		Through study completion, up to 4 months
Secondary	Time to reach maximum plasma concentration (tmax) of TW001		Through study completion, up to 4 months