ANAVEX2-73 for Treatment of Early Alzheimer's Disease

NCT03790709 | Completed Phase 2

• 1 other identifier: ANAVEX2-73-AD-004
• Study Type: interventional
• Target: 509
• Locations: 5 countries
• Sites: 54

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)

  Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog)

  48 weeks

• ADCS-ADL (Activities of Daily Living)

  Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL)

  48 weeks

Secondary Outcomes (2)

• CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)

  48 weeks

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  48 weeks

Other Outcomes (5)

• Number of participants with change of brain volume assessed by MRI

  48 weeks

• Blood assessment

  48 weeks

• CSF assessment

  48 weeks

Study Arms (3)

High dose ANAVEX2-73

EXPERIMENTAL

High dose active once daily orally

Drug: High dose ANAVEX2-73

Mid dose ANAVEX2-73

EXPERIMENTAL

Mid dose active once daily orally

Drug: Mid dose ANAVEX2-73

Placebo oral capsule

PLACEBO COMPARATOR

Placebo dose once daily orally

Drug: Placebo oral capsule

Interventions

High dose ANAVEX2-73 DRUG

Oral capsule

High dose ANAVEX2-73

Mid dose ANAVEX2-73 DRUG

Oral capsule

Mid dose ANAVEX2-73

Placebo oral capsule DRUG

Oral capsule

Placebo oral capsule

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Historical records of amyloid CSF assessment or
• Historical records of amyloid PET scan or
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anavex Life Sciences Corp.: lead
• Anavex Australia Pty Ltd.: collaborator
• Anavex Germany GmbH: collaborator
• Anavex Canada Ltd.: collaborator

Study Sites (54)

Central Coast Neurosciences Research

Central Coast, New South Wales, Australia

Location

Hornsby (Northern Sydney Health)

Hornsby, New South Wales, Australia

Location

KaRa MINDS

Macquarie Park, New South Wales, Australia

Location

St Vincent Hospital Sydney

Sydney, New South Wales, Australia

Location

University of Sydney

Sydney, New South Wales, Australia

Location

Gold Coast Memory Disorders Clinic

Southport, Quennsland, Australia

Location

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

Adelaide, South Australia, Australia

Location

Penninsula Therapeutic and Research Group

Frankston, Victoria, Australia

Location

Geelong Private Medical Centre

Geelong, Victoria, Australia

Location

Delmont Private Hospital

Glen Iris, Victoria, Australia

Location

Hammond Care

Malvern, Victoria, Australia

Location

Alfred Health

Melbourne, Victoria, Australia

Location

Austin Health

Melbourne, Victoria, Australia

Location

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, Australia

Location

Royal Melbourne Hospital (RMH)

Parkville, Victoria, Australia

Location

McCusker

Nedlands, Western Australia, Australia

Location

Healthy Brain Aging Labs Uni of Calgary

Calgary, Alberta, Canada

Location

University of British Columbia Hospital

Vancouver, British Columbia, Canada

Location

Vancouver Island Health Authority

Victoria, British Columbia, Canada

Location

True North Clinical Research

Halifax, Nova Scotia, Canada

Location

True North Clinical Research

Kentville, Nova Scotia, Canada

Location

Parkwood Institute

London, Ontario, Canada

Location

Bruyere Continuing Care

Ottawa, Ontario, Canada

Location

Kawartha Centre

Peterborough, Ontario, Canada

Location

Bay Crest Health Sciences

Toronto, Ontario, Canada

Location

Toronto Memory Program

Toronto, Ontario, Canada

Location

Toronto Western Hospital

Toronto, Ontario, Canada

Location

University of Ulm, Memory Clinic

Ulm, Baden-Wurttemberg, Germany

Location

Bayreuth Clinic, Hohe Warte Hospital

Bayreuth, Bavaria, Germany

Location

Technical University of Munich, School of Medicine

München, Bavaria, Germany

Location

Central Institute of Mental Health

Mannheim, Hesse, Germany

Location

Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy

Göttingen, Lower Saxony, Germany

Location

University Hospital, Bonn

Bonn, North Rhine-Westphalia, Germany

Location

Clinic for Psychiatry and Psychotherapy

Mainz, Rhineland-Palatinate, Germany

Location

Charite University Medicine

Berlin, Germany

Location

Brain Research Center

's-Hertogenbosch, Netherlands

Location

Brain Research Center

Amsterdam, Netherlands

Location

Brain Research Center

Zwolle, Netherlands

Location

MAC Clinical Research

Teesside, County Teesside, United Kingdom

Location

University of Edinburgh

Edinburgh, Scotland, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, Scotland, United Kingdom

Location

Cognition Health

Guildford, Surrey, United Kingdom

Location

MAC Clinical Research

Barnsley, United Kingdom

Location

Cognition Health

Birmingham, United Kingdom

Location

MAC Clinical Research

Blackpool, United Kingdom

Location

MAC Clinical Research

Cannock, United Kingdom

Location

MAC Clinical Research

Leeds, United Kingdom

Location

MAC Clinical Research

Liverpool, United Kingdom

Location

Cognition Health

London, United Kingdom

Location

Imperial College

London, United Kingdom

Location

King's College

London, United Kingdom

Location

MAC Clinical Research

Manchester, United Kingdom

Location

Cognition Health

Plymouth, United Kingdom

Location

Southern Health NHS Foundation Trust

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

tetrahydro-N, N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: There will be blinding procedures for this study. Capsules will be indistinguishable from active ingridient containing capsules.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: January 2, 2019
• Study Start: July 3, 2018
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2022
• Last Updated: July 14, 2022

Record last verified: 2022-07

Locations

AU (16); DE (8); NL (3); CA (11); GB (16)