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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03790709




Registration number
NCT03790709
Ethics application status
Date submitted
24/12/2018
Date registered
1/01/2019
Date last updated
6/08/2019

Titles & IDs
Public title
ANAVEX2-73 for Treatment of Early Alzheimer's Disease
Scientific 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)
Secondary ID [1] 0 0
ANAVEX2-73-AD-004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - High dose ANAVEX2-73
Treatment: Drugs - Mid dose ANAVEX2-73
Treatment: Drugs - Placebo oral capsule

Experimental: High dose ANAVEX2-73 - High dose active once daily orally

Experimental: Mid dose ANAVEX2-73 - Mid dose active once daily orally

Placebo Comparator: Placebo oral capsule - Placebo dose once daily orally


Treatment: Drugs: High dose ANAVEX2-73
Oral capsule

Treatment: Drugs: Mid dose ANAVEX2-73
Oral capsule

Treatment: Drugs: Placebo oral capsule
Oral capsule

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) - Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo
Timepoint [1] 0 0
48 weeks
Primary outcome [2] 0 0
ADCS-ADL (Activities of Daily Living) - Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo
Timepoint [2] 0 0
48 weeks
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) - Change from baseline to week 48 on Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo
Timepoint [2] 0 0
48 weeks
Secondary outcome [3] 0 0
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)
Timepoint [3] 0 0
Weeks 0, 4, 12, 24, 36, and 48

Eligibility
Key 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.
Minimum age
60 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QuennslandSA,VIC,WA
Recruitment hospital [1] 0 0
Central Coast Neurosciences Research - Central Coast
Recruitment hospital [2] 0 0
Hornsby (Northern Sydney Health) - Hornsby
Recruitment hospital [3] 0 0
KaRa MINDS - Macquarie Park
Recruitment hospital [4] 0 0
St Vincent Hospital Sydney - Sydney
Recruitment hospital [5] 0 0
University of Sydney - Sydney
Recruitment hospital [6] 0 0
Gold Coast Memory Disorders Clinic - Southport
Recruitment hospital [7] 0 0
The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH) - Adelaide
Recruitment hospital [8] 0 0
Penninsula Therapeutic and Research Group - Frankston
Recruitment hospital [9] 0 0
Geelong Private Medical Centre - Geelong
Recruitment hospital [10] 0 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [11] 0 0
Hammond Care - Malvern
Recruitment hospital [12] 0 0
Alfred Health - Melbourne
Recruitment hospital [13] 0 0
Austin Health - Melbourne
Recruitment hospital [14] 0 0
Monash Alfred Psychiatry Research Centre - Melbourne
Recruitment hospital [15] 0 0
Royal Melbourne Hospital (RMH) - Parkville
Recruitment hospital [16] 0 0
McCusker - Nedlands
Recruitment postcode(s) [1] 0 0
- Central Coast
Recruitment postcode(s) [2] 0 0
- Hornsby
Recruitment postcode(s) [3] 0 0
- Macquarie Park
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment postcode(s) [5] 0 0
- Southport
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Frankston
Recruitment postcode(s) [8] 0 0
- Geelong
Recruitment postcode(s) [9] 0 0
- Glen Iris
Recruitment postcode(s) [10] 0 0
- Malvern
Recruitment postcode(s) [11] 0 0
- Melbourne
Recruitment postcode(s) [12] 0 0
- Parkville
Recruitment postcode(s) [13] 0 0
- Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Anavex Life Sciences Corp.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Anavex Australia Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03790709
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Director
Address 0 0
Country 0 0
Phone 0 0
844-689-3939
Fax 0 0
Email 0 0
alz@anavex.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03790709