ANAVEX2-73 for Treatment of Early Alzheimer's Disease

• Sponsor: Anavex Life Sciences Corp. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03790709
• Collaborator: Anavex Australia Pty Ltd. (Industry), Anavex Germany GmbH (Industry), Anavex Canada Ltd. (Other)
• Enrollment: 509
• Locations: 54
• Arms: 3
• Actual Duration (Months): 47.9
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: High dose ANAVEX2-73; Drug: Mid dose ANAVEX2-73; Drug: Placebo oral capsule	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 509 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized 1:1:1 to two different ANAVEX2-73 doses or placeboRandomized 1:1:1 to two different ANAVEX2-73 doses or placebo
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: There will be blinding procedures for this study. Capsules will be indistinguishable from active ingridient containing capsules.
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jul 3, 2018
• Actual Primary Completion Date: Jun 30, 2022
• Actual Study Completion Date: Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: High dose ANAVEX2-73 High dose active once daily orally	Drug: High dose ANAVEX2-73; Oral capsule
Experimental: Mid dose ANAVEX2-73 Mid dose active once daily orally	Drug: Mid dose ANAVEX2-73; Oral capsule
Placebo Comparator: Placebo oral capsule Placebo dose once daily orally	Drug: Placebo oral capsule; Oral capsule

Outcome Measures

Primary Outcome Measures

1. ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [48 weeks]

   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)

2. ADCS-ADL (Activities of Daily Living) [48 weeks]

   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)

Secondary Outcome Measures

1. CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) [48 weeks]

   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)

2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [48 weeks]

   Assess the safety and tolerability of ANAVEX2-73 compared to placebo

Other Outcome Measures

1. Number of participants with change of brain volume assessed by MRI [48 weeks]

   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

2. Blood assessment [48 weeks]

   Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration

3. CSF assessment [48 weeks]

   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

4. Number of participants with pre-specified genetic variants [48 weeks]

   AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed

5. RSCAQ sleep score [Weeks 0, 4, 12, 24, 36, and 48]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Coast Neurosciences Research	Central Coast	New South Wales	Australia
2	Hornsby (Northern Sydney Health)	Hornsby	New South Wales	Australia
3	KaRa MINDS	Macquarie Park	New South Wales	Australia
4	St Vincent Hospital Sydney	Sydney	New South Wales	Australia
5	University of Sydney	Sydney	New South Wales	Australia
6	Gold Coast Memory Disorders Clinic	Southport	Quennsland	Australia
7	The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)	Adelaide	South Australia	Australia
8	Penninsula Therapeutic and Research Group	Frankston	Victoria	Australia
9	Geelong Private Medical Centre	Geelong	Victoria	Australia
10	Delmont Private Hospital	Glen Iris	Victoria	Australia
11	Hammond Care	Malvern	Victoria	Australia
12	Alfred Health	Melbourne	Victoria	Australia
13	Austin Health	Melbourne	Victoria	Australia
14	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria	Australia
15	Royal Melbourne Hospital (RMH)	Parkville	Victoria	Australia
16	McCusker	Nedlands	Western Australia	Australia
17	Healthy Brain Aging Labs Uni of Calgary	Calgary	Alberta	Canada
18	University of British Columbia Hospital	Vancouver	British Columbia	Canada
19	Vancouver Island Health Authority	Victoria	British Columbia	Canada
20	True North Clinical Research	Halifax	Nova Scotia	Canada
21	True North Clinical Research	Kentville	Nova Scotia	Canada
22	Parkwood Institute	London	Ontario	Canada
23	Bruyere Continuing Care	Ottawa	Ontario	Canada
24	Kawartha Centre	Peterborough	Ontario	Canada
25	Bay Crest Health Sciences	Toronto	Ontario	Canada
26	Toronto Memory Program	Toronto	Ontario	Canada
27	Toronto Western Hospital	Toronto	Ontario	Canada
28	University of Ulm, Memory Clinic	Ulm	Baden-Wuerttemberg	Germany
29	Bayreuth Clinic, Hohe Warte Hospital	Bayreuth	Bavaria	Germany
30	Technical University of Munich, School of Medicine	München	Bavaria	Germany
31	Central Institute of Mental Health	Mannheim	Hessen	Germany
32	Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy	Göttingen	Lower Saxony	Germany
33	University Hospital, Bonn	Bonn	North Rhine-Westphalia	Germany
34	Clinic for Psychiatry and Psychotherapy	Mainz	Rheinland-Pfalz	Germany
35	Charite University Medicine	Berlin		Germany
36	Brain Research Center	Amsterdam		Netherlands
37	Brain Research Center	Den Bosch		Netherlands
38	Brain Research Center	Zwolle		Netherlands
39	MAC Clinical Research	Teesside	County Teesside	United Kingdom
40	University of Edinburgh	Edinburgh	Scotland	United Kingdom
41	Glasgow Memory Clinic	Glasgow	Scotland	United Kingdom
42	Cognition Health	Guildford	Surrey	United Kingdom
43	MAC Clinical Research	Barnsley		United Kingdom
44	Cognition Health	Birmingham		United Kingdom
45	MAC Clinical Research	Blackpool		United Kingdom
46	MAC Clinical Research	Cannock		United Kingdom
47	MAC Clinical Research	Leeds		United Kingdom
48	MAC Clinical Research	Liverpool		United Kingdom
49	Cognition Health	London		United Kingdom
50	Imperial College	London		United Kingdom
51	King's College	London		United Kingdom
52	MAC Clinical Research	Manchester		United Kingdom
53	Cognition Health	Plymouth		United Kingdom
54	Southern Health NHS Foundation Trust	Southampton		United Kingdom

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anavex Life Sciences Corp.
• ClinicalTrials.gov Identifier: NCT03790709
• Other Study ID Numbers: ANAVEX2-73-AD-004
• First Posted: Jan 2, 2019
• Last Update Posted: Jul 14, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

No Results Posted as of Jul 14, 2022