ANAVEX2-73 for Treatment of Early Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

A Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled 48-week Safety and Efficacy Trial of ANAVEX2-73 for the Treatment of Early Alzheimer's Disease (AD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03790709
• Other study ID #: ANAVEX2-73-AD-004
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 3, 2018
• Est. completion date: June 30, 2022

Study information

• Verified date: July 2022
• Source: Anavex Life Sciences Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 509
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• High dose ANAVEX2-73
Oral capsule
• Mid dose ANAVEX2-73
Oral capsule
• Placebo oral capsule
Oral capsule

Locations

Country	Name	City	State
Australia	The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)	Adelaide	South Australia
Australia	Central Coast Neurosciences Research	Central Coast	New South Wales
Australia	Penninsula Therapeutic and Research Group	Frankston	Victoria
Australia	Geelong Private Medical Centre	Geelong	Victoria
Australia	Delmont Private Hospital	Glen Iris	Victoria
Australia	Hornsby (Northern Sydney Health)	Hornsby	New South Wales
Australia	KaRa MINDS	Macquarie Park	New South Wales
Australia	Hammond Care	Malvern	Victoria
Australia	Alfred Health	Melbourne	Victoria
Australia	Austin Health	Melbourne	Victoria
Australia	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria
Australia	McCusker	Nedlands	Western Australia
Australia	Royal Melbourne Hospital (RMH)	Parkville	Victoria
Australia	Gold Coast Memory Disorders Clinic	Southport	Quennsland
Australia	St Vincent Hospital Sydney	Sydney	New South Wales
Australia	University of Sydney	Sydney	New South Wales
Canada	Healthy Brain Aging Labs Uni of Calgary	Calgary	Alberta
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 British Columbia Hospital	Vancouver	British Columbia
Canada	Vancouver Island Health Authority	Victoria	British Columbia
Germany	Bayreuth Clinic, Hohe Warte Hospital	Bayreuth	Bavaria
Germany	Charite University Medicine	Berlin
Germany	University Hospital, Bonn	Bonn	North Rhine-Westphalia
Germany	Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy	Göttingen	Lower Saxony
Germany	Clinic for Psychiatry and Psychotherapy	Mainz	Rheinland-Pfalz
Germany	Central Institute of Mental Health	Mannheim	Hessen
Germany	Technical University of Munich, School of Medicine	München	Bavaria
Germany	University of Ulm, Memory Clinic	Ulm	Baden-Wuerttemberg
Netherlands	Brain Research Center	Amsterdam
Netherlands	Brain Research Center	Den Bosch
Netherlands	Brain Research Center	Zwolle
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	University of Edinburgh	Edinburgh	Scotland
United Kingdom	Glasgow Memory Clinic	Glasgow	Scotland
United Kingdom	Cognition Health	Guildford	Surrey
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	MAC Clinical Research	Teesside	County Teesside

Sponsors (4)

Lead Sponsor	Collaborator
Anavex Life Sciences Corp.	Anavex Australia Pty Ltd., Anavex Canada Ltd., Anavex Germany GmbH

Countries where clinical trial is conducted

Australia,  Canada,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with change of brain volume assessed by MRI	To evaluate the effect of ANAVEX2-73 on structural and Arterial Spin Labeling (ASL) MRI scan assessments characteristic for AD pathophysiology compared to placebo over a 48-week treatment duration	48 weeks
Other	Blood assessment	Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration	48 weeks
Other	CSF assessment	Changes in CSF parameters (Abeta40, Abeta42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 concentration) characteristic for AD pathophysiology from baseline and compared to placebo at; +48 weekstreatment differences within subgroups will be performed	48 weeks
Other	Number of participants with pre-specified genetic variants	AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed	48 weeks
Other	RSCAQ sleep score	To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess reported sleep continuity (RSCAQ)	Weeks 0, 4, 12, 24, 36, and 48
Primary	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
Primary	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	CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)	Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared with placebo using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)	48 weeks
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.03	Assess the safety and tolerability of ANAVEX2-73 compared to placebo	48 weeks