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History of Changes for Study: NCT03790709
ANAVEX2-73 for Treatment of Early Alzheimer's Disease
Latest version (submitted July 12, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 31, 2018 None (earliest Version on record)
2 August 4, 2019 Contacts/Locations and Study Status
3 November 17, 2019 Study Status
4 July 24, 2020 Study Status, Contacts/Locations and Sponsor/Collaborators
5 September 1, 2020 Contacts/Locations and Study Status
6 September 8, 2020 Contacts/Locations and Study Status
7 October 12, 2020 Study Status and Contacts/Locations
8 October 20, 2020 Contacts/Locations and Study Status
9 October 26, 2020 Contacts/Locations and Study Status
10 November 2, 2020 Study Status and Contacts/Locations
11 November 19, 2020 Contacts/Locations and Study Status
12 December 2, 2020 Study Status and Contacts/Locations
13 December 8, 2020 Contacts/Locations and Study Status
14 January 7, 2021 Study Status and Contacts/Locations
15 January 19, 2021 Contacts/Locations and Study Status
16 February 1, 2021 Contacts/Locations and Study Status
17 February 2, 2021 Contacts/Locations and Study Status
18 February 3, 2021 Contacts/Locations and Study Status
19 February 22, 2021 Contacts/Locations and Study Status
20 March 2, 2021 Study Status and Contacts/Locations
21 March 9, 2021 Contacts/Locations and Study Status
22 March 24, 2021 Contacts/Locations and Study Status
23 March 26, 2021 Contacts/Locations and Study Status
24 April 3, 2021 Study Status and Contacts/Locations
25 April 6, 2021 Contacts/Locations and Study Status
26 April 8, 2021 Contacts/Locations and Study Status
27 April 19, 2021 Contacts/Locations and Study Status
28 April 29, 2021 Contacts/Locations and Study Status
29 September 26, 2021 Recruitment Status, Study Status, Contacts/Locations and Study Design
30 July 12, 2022 Recruitment Status, Study Status and Outcome Measures
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Study NCT03790709
Submitted Date:  December 31, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: ANAVEX2-73-AD-004
Brief Title: ANAVEX2-73 for Treatment of Early Alzheimer's Disease
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2018
Overall Status: Recruiting
Study Start: July 3, 2018
Primary Completion: December 31, 2020 [Anticipated]
Study Completion: March 31, 2021 [Anticipated]
First Submitted: December 24, 2018
First Submitted that
Met QC Criteria:
December 31, 2018
First Posted: January 2, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
December 31, 2018
Last Update Posted: January 2, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Anavex Life Sciences Corp.
Responsible Party: Sponsor
Collaborators: Anavex Australia Pty Ltd.
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module 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.
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.
Open or close this module Conditions
Conditions: Alzheimer Disease
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2/Phase 3
Interventional Study Model: Parallel Assignment
Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo
Number of Arms: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 450 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)
[ Time Frame: 48 weeks ]

Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo
2. ADCS-ADL (Activities of Daily Living)
[ Time Frame: 48 weeks ]

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
Secondary Outcome Measures:
1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
[ Time Frame: 48 weeks ]

Assess the safety and tolerability of ANAVEX2-73 compared to placebo
2. CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)
[ Time Frame: 48 weeks ]

Change from baseline to week 48 on Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo
3. RSCAQ sleep score
[ Time Frame: 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)
Other Outcome Measures:
1. Number of participants with change of brain volume assessed by MRI
[ Time Frame: 48 weeks ]

Structural (and optional ASL) MRI scan assessments characteristic for AD pathophysiology from baseline and compared to placebo at +48 weeks
2. Blood assessment
[ Time Frame: 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
[ Time Frame: 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
[ Time Frame: 48 weeks ]

AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed
Open or close this module Eligibility
Minimum Age: 60 Years
Maximum Age: 85 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.
Open or close this module Contacts/Locations
Central Contact Person: Study Director
Telephone: 844-689-3939
Email: alz@anavex.com
Locations: Australia, New South Wales
Hornsby (Northern Sydney Health)
[Recruiting]
Hornsby, New South Wales, Australia
Contact:Contact: Susan Kurrle, Prof
KaRa MINDS
[Recruiting]
Macquarie Park, New South Wales, Australia
Contact:Contact: Rosalyn Lai, Dr
Australia, South Australia
The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)
[Recruiting]
Adelaide, South Australia, Australia
Contact:Contact: Cathy Short, Dr
Australia, Victoria
Penninsula Therapeutic and Research Group
[Recruiting]
Frankston, Victoria, Australia
Contact:Contact: Jennifer Grunfeld, Dr
Geelong Private Medical Centre
[Recruiting]
Geelong, Victoria, Australia
Contact:Contact: Alastair Mander, A/Prof
Delmont Private Hospital
[Recruiting]
Glen Iris, Victoria, Australia
Contact:Contact: Peter Drysdale, Dr
Hammond Care
[Recruiting]
Malvern, Victoria, Australia
Contact:Contact: Stephen Macfarlane, A/Prof
Royal Melbourne Hospital (RMH)
[Recruiting]
Parkville, Victoria, Australia
Contact:Contact: Amy Brodtmann, A/Prof
Australia, Western Australia
McCusker
[Recruiting]
Nedlands, Western Australia, Australia
Contact:Contact: Roger Clarnette, A/Prof
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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