ANAVEX2-73 for Treatment of Early Alzheimer's Disease

NCT ID: NCT03790709

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 509 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-03
• Study Completion Date: 2022-06-30

Brief Summary

Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and function after 48 weeks of daily treatment. Additional outcome measures include refined measures of sleep, behavioral and psychological symptoms typically observed in AD, changes in daily functioning of participants and changes in caregiver burden, as well as changes in quality of life measures of both, patients and caregivers during treatment with ANAVEX2-73.

Detailed Description

This is a Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and function after 48 weeks of daily treatment. Additional outcome measures include refined measures of sleep, behavioral and psychological symptoms typically observed in AD, changes in daily functioning of participants and changes in caregiver burden, as well as changes in quality of life measures of both, patients and caregivers during treatment with ANAVEX2-73. In addition, safety assessments, pharmacokinetic (PK) assessments and collections of CSF and blood markers of AD pathophysiology before and after treatment will be performed.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

High dose ANAVEX2-73

High dose active once daily orally

Group Type: EXPERIMENTAL

High dose ANAVEX2-73

Intervention Type: DRUG

Oral capsule

Mid dose ANAVEX2-73

Mid dose active once daily orally

Group Type: EXPERIMENTAL

Mid dose ANAVEX2-73

Intervention Type: DRUG

Oral capsule

Placebo oral capsule

Placebo dose once daily orally

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

Oral capsule

Interventions

High dose ANAVEX2-73

Oral capsule

Intervention Type: DRUG

Mid dose ANAVEX2-73

Oral capsule

Intervention Type: DRUG

Placebo oral capsule

Oral capsule

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients aged 60 to 85 years, inclusive, with a NIA-AA diagnosis of mild cognitive impairment (MCI) due to AD or early stage mild dementia due to AD. AD diagnosis should be made by an appropriately qualified medical specialist and AD pathology should be confirmed by either:

1. Historical records of amyloid CSF assessment or

2. Historical records of amyloid PET scan or

3. If neither historical records are available, then AD pathological diagnosis confirmation should be offered at screening:

i. CSF collection or ii. Amyloid PET iii. Past medical records of MRI or CT are optional.

• Mini Mental State Examination (MMSE) score between 20-28, inclusive.
• Free Recall score ≤17 or Total Recall score <40 on the Free and Cued Selective Reminding Test (FCSRT).
• Participants are either outpatients, or residents of an assisted-living facility. Participant has a designated study partner, who spends at least 10hrs per week with the participant, in order that assessments e.g. carer burden instruments are completed with true knowledge of the participant.
• No suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought(s) with intent but without specific plan, or active suicidal thought(s) with plan and intent) OR suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).
• Confirmation from the participant that, if of childbearing potential is not pregnant through urine pregnancy testing.

Exclusion Criteria

• Patients who have a progressive medical or neurological condition that in the opinion of the investigator would interfere with the conduct of the study. Exception: If diagnosed with seizures, must be on stable anti-seizure medication for at least 3 months prior to screening.
• Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
• History or clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque.
• History of neurologic (e.g. stroke, traumatic brain injury) or psychiatric condition that the investigator deems may interfere with interpretability of data.
• History of untreated thyroid disorder, Type 1 diabetes, and insulin dependent or uncontrolled Type II diabetes, as determined by the investigator (e.g. non-insulin-controlled Type II diabetes, whose HbA1c value is higher than 8.0%).
• Body Mass Index (BMI) > 30.
• History of clinical hepatic dysfunction.
• Current symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hematological or hormonal disorders.
• Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal (ULN) as determined during screening.
• Significant history of drug addiction (with the exception of nicotine dependence) or abuse (including alcohol, as defined in DSM-V or in the opinion of the investigator) within the last two years prior to informed consent, or a positive urine drug screen for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at screening. Prescription medication yielding a positive drug screen are acceptable except for tricyclic antidepressants (e.g. Amitriptyline, Amoxapine, Desipramine, (Norpramin) Doxepin, Imipramine (Tofranil), Nortriptyline (Pamelor), Protriptyline (Vivactil), Trimipramine (Surmontil)).
• Clinically significant infection within the last 30 days prior screening (e.g., chronic persistent or acute infection, urinary tract infections (UTI)).
• Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
• Myocardial infarction within the last year.
• History of cancer within the last 3 years, with the exception of basal cell carcinoma and non-metastatic squamous cell carcinoma of the skin and prostate cancer with currently normal PSA.
• Other clinically significant abnormality on physical, neurological, laboratory, or electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the participant.
• Hemoglobin < 11 g/dL.
• Have any contraindication to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in skull and cardiac devices or severe claustrophobia).
• Smoking > 1 pack of cigarettes per day (as assessed for the 30 days prior to screening).
• Alcohol use of more than 2 drinks per day.
• Current use of over-the-counter (OTC) supplements or nutraceuticals unless they are on stable dose for at least 3 months prior to screening and are documented in the eCRF.
• Use of over the counter (OTC) or prescription medication for sleep on 2 or more occasions per week.
• Being treated with psychoactive medications on a stable dose for less than 3 month.
• Any prior exposure to ANAVEX2-73.
• Individuals enrolled in previous AD clinical trial involving an investigational drug treatment less than 3 months ago (longer than 3 month ago allowed).
• Any known hypersensitivity to any of the excipients contained in the study drug formulation.
• Any other criteria (such as a clinically significant screening blood test result), which in the opinion of the Investigator causes the participant not to qualify for the study.
• Evidence of cerebrovascular dementia with a Hachinski score of 4 or more.

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Anavex Australia Pty Ltd.

INDUSTRY

Sponsor Role: collaborator

Anavex Germany GmbH

INDUSTRY

Sponsor Role: collaborator

Anavex Canada Ltd.

UNKNOWN

Sponsor Role: collaborator

Anavex Life Sciences Corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Central Coast Neurosciences Research

Central Coast, New South Wales, Australia

Hornsby (Northern Sydney Health)

Hornsby, New South Wales, Australia

KaRa MINDS

Macquarie Park, New South Wales, Australia

St Vincent Hospital Sydney

Sydney, New South Wales, Australia

University of Sydney

Sydney, New South Wales, Australia

Gold Coast Memory Disorders Clinic

Southport, Quennsland, Australia

The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)

Adelaide, South Australia, Australia

Penninsula Therapeutic and Research Group

Frankston, Victoria, Australia

Geelong Private Medical Centre

Geelong, Victoria, Australia

Delmont Private Hospital

Glen Iris, Victoria, Australia

Hammond Care

Malvern, Victoria, Australia

Alfred Health

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, Australia

Royal Melbourne Hospital (RMH)

Parkville, Victoria, Australia

McCusker

Nedlands, Western Australia, Australia

Healthy Brain Aging Labs Uni of Calgary

Calgary, Alberta, Canada

University of British Columbia Hospital

Vancouver, British Columbia, Canada

Vancouver Island Health Authority

Victoria, British Columbia, Canada

True North Clinical Research

Halifax, Nova Scotia, Canada

True North Clinical Research

Kentville, Nova Scotia, Canada

Parkwood Institute

London, Ontario, Canada

Bruyere Continuing Care

Ottawa, Ontario, Canada

Kawartha Centre

Peterborough, Ontario, Canada

Bay Crest Health Sciences

Toronto, Ontario, Canada

Toronto Memory Program

Toronto, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

University of Ulm, Memory Clinic

Ulm, Baden-Wurttemberg, Germany

Bayreuth Clinic, Hohe Warte Hospital

Bayreuth, Bavaria, Germany

Technical University of Munich, School of Medicine

München, Bavaria, Germany

Central Institute of Mental Health

Mannheim, Hesse, Germany

Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy

Göttingen, Lower Saxony, Germany

University Hospital, Bonn

Bonn, North Rhine-Westphalia, Germany

Clinic for Psychiatry and Psychotherapy

Mainz, Rhineland-Palatinate, Germany

Charite University Medicine

Berlin, , Germany

Brain Research Center

's-Hertogenbosch, , Netherlands

Brain Research Center

Amsterdam, , Netherlands

Brain Research Center

Zwolle, , Netherlands

MAC Clinical Research

Teesside, County Teesside, United Kingdom

University of Edinburgh

Edinburgh, Scotland, United Kingdom

Glasgow Memory Clinic

Glasgow, Scotland, United Kingdom

Cognition Health

Guildford, Surrey, United Kingdom

MAC Clinical Research

Barnsley, , United Kingdom

Cognition Health

Birmingham, , United Kingdom

MAC Clinical Research

Blackpool, , United Kingdom

MAC Clinical Research

Cannock, , United Kingdom

MAC Clinical Research

Leeds, , United Kingdom

MAC Clinical Research

Liverpool, , United Kingdom

Cognition Health

London, , United Kingdom

Imperial College

London, , United Kingdom

King's College

London, , United Kingdom

MAC Clinical Research

Manchester, , United Kingdom

Cognition Health

Plymouth, , United Kingdom

Southern Health NHS Foundation Trust

Southampton, , United Kingdom

Countries

Australia; Canada; Germany; Netherlands; United Kingdom

Other Identifiers

ANAVEX2-73-AD-004

Identifier Type: -

Identifier Source: org_study_id