Clinical Trials/NCT05323812

NCT05323812

Completed

Phase 2

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

Treeway B.V.6 sites in 2 countries61 target enrollmentMarch 1, 2023

ConditionsAlzheimer Disease

InterventionsPlacebo TW001

DrugsTW001 Placebo

Overview

Phase: Phase 2
Intervention: Placebo
Conditions: Alzheimer Disease
Sponsor: Treeway B.V.
Enrollment: 61
Locations: 6
Primary Endpoint: Plasma oxidative stress biomarkers
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

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.

Registry

clinicaltrials.gov

Start Date

March 1, 2023

End Date

December 30, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Treeway B.V.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

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.

Arms & Interventions

Placebo

Intervention: Placebo

TW001

Intervention: TW001

Outcomes

Primary Outcomes

Plasma oxidative stress biomarkers

Time Frame: 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

Time Frame: Through study completion, up to 4 months

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

Nature, frequency and severity of adverse events

Time Frame: Through study completion, up to 4 months

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

Secondary Outcomes

Time to reach maximum plasma concentration (tmax) of TW001(Through study completion, up to 4 months)
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)