Clinical trial NCT03790709: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer Disease
Lead sponsor: Anavex Life Sciences Corp.
Sponsor class: INDUSTRY
Collaborators: name: Anavex Australia Pty Ltd.
name: Anavex Germany GmbH
name: Anavex Canada Ltd.
First posted: 2019-01-02
Enrollment: 509
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)
timeFrame: 48 weeks
measure: ADCS-ADL (Activities of Daily Living)
timeFrame: 48 weeks
Secondary outcomes:
measure: CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)
timeFrame: 48 weeks
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: 48 weeks
Other outcomes:
measure: Number of participants with change of brain volume assessed by MRI
timeFrame: 48 weeks
measure: Blood assessment
timeFrame: 48 weeks
measure: CSF assessment
timeFrame: 48 weeks
measure: Number of participants with pre-specified genetic variants
timeFrame: 48 weeks
measure: RSCAQ sleep score
timeFrame: Weeks 0, 4, 12, 24, 36, and 48
Locations:
city: Central Coast
country: Australia
facility: Central Coast Neurosciences Research
state: New South Wales
city: Hornsby
country: Australia
facility: Hornsby (Northern Sydney Health)
state: New South Wales
city: Macquarie Park
country: Australia
facility: KaRa MINDS
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent Hospital Sydney
state: New South Wales
city: Sydney
country: Australia
facility: University of Sydney
state: New South Wales
city: Southport
country: Australia
facility: Gold Coast Memory Disorders Clinic
state: Quennsland
city: Adelaide
country: Australia
facility: The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)
state: South Australia
city: Frankston
country: Australia
facility: Penninsula Therapeutic and Research Group
state: Victoria
city: Geelong
country: Australia
facility: Geelong Private Medical Centre
state: Victoria
city: Glen Iris
country: Australia
facility: Delmont Private Hospital
state: Victoria
city: Malvern
country: Australia
facility: Hammond Care
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Monash Alfred Psychiatry Research Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Nedlands
country: Australia
facility: McCusker
state: Western Australia
city: Calgary
country: Canada
facility: Healthy Brain Aging Labs Uni of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Vancouver Island Health Authority
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: Kentville
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Ottawa
country: Canada
facility: Bruyere Continuing Care
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Centre
state: Ontario
city: Toronto
country: Canada
facility: Bay Crest Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Ulm
country: Germany
facility: University of Ulm, Memory Clinic
state: Baden-Wuerttemberg
city: Bayreuth
country: Germany
facility: Bayreuth Clinic, Hohe Warte Hospital
state: Bavaria
city: München
country: Germany
facility: Technical University of Munich, School of Medicine
state: Bavaria
city: Mannheim
country: Germany
facility: Central Institute of Mental Health
state: Hessen
city: Göttingen
country: Germany
facility: Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy
state: Lower Saxony
city: Bonn
country: Germany
facility: University Hospital, Bonn
state: North Rhine-Westphalia
city: Mainz
country: Germany
facility: Clinic for Psychiatry and Psychotherapy
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charite University Medicine
city: Amsterdam
country: Netherlands
facility: Brain Research Center
city: Den Bosch
country: Netherlands
facility: Brain Research Center
city: Zwolle
country: Netherlands
facility: Brain Research Center
city: Teesside
country: United Kingdom
facility: MAC Clinical Research
state: County Teesside
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
state: Scotland
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic
state: Scotland
city: Guildford
country: United Kingdom
facility: Cognition Health
state: Surrey
city: Barnsley
country: United Kingdom
facility: MAC Clinical Research
city: Birmingham
country: United Kingdom
facility: Cognition Health
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research
city: Cannock
country: United Kingdom
facility: MAC Clinical Research
city: Leeds
country: United Kingdom
facility: MAC Clinical Research
city: Liverpool
country: United Kingdom
facility: MAC Clinical Research
city: London
country: United Kingdom
facility: Cognition Health
city: London
country: United Kingdom
facility: Imperial College
city: London
country: United Kingdom
facility: King's College
city: Manchester
country: United Kingdom
facility: MAC Clinical Research
city: Plymouth
country: United Kingdom
facility: Cognition Health
city: Southampton
country: United Kingdom
facility: Southern Health NHS Foundation Trust
Study officials:
References: