Clinical trial NCT05531526: Phase 3, Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants With Early Alzheimer's Disease (Polaris-AD)
Official title: A Phase 3 Double-blind, Randomized, Placebo-controlled, Multi-center Trial to Evaluate the Efficacy and Safety of AR1001 Over 52 Weeks in Participants With Early Alzheimer's Disease (Polaris-AD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: AR1001
AD
Early AD
Lead sponsor: AriBio Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-09-08
Enrollment: 1150
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Phase 3 Double-blind, Randomized, Placebo-controlled, Multi-center Trial to Evaluate the Efficacy and Safety of AR1001 over 52 Weeks in Participants with Early Alzheimer's Disease
Primary purpose: TREATMENT

Brief summary: This AR1001-ADP3-US01 protocol is a double-blind, randomized, placebo-controlled, multi- center, parallel-group comparison pivotal Phase 3 study to evaluate the efficacy and safety of AR1001 for the treatment of participants with early AD.

Detailed description: The purpose of this Study is to evaluate the efficacy and safety of AR1001 in participants with Early Alzheimer's Disease (AD).

AR1001 is a small molecule that has demonstrated its potential as a therapeutic agent for AD via its polypharmacological characteristics with multiple mechanisms to ameliorate AD pathology.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants aged 55 to 90 years of age inclusive at the time of signing the informed consent form
2. Mild cognitive impairment or mild dementia consistent with AD defined by stages 3 to 4 according to the National Institute on Aging and Alzheimer's Association (NIA-AA) at Screening
3. Participants with a history of subjective cognitive and memory decline with onset within 5 years before Screening, confirmed by study partner.
4. Participants who have a MMSE score greater than or equal to 20
5. Participants with a CDR global rating of 0.5 or 1
6. Participants with a RBANS score based on the Delayed Memory Index (DMI) score less than or equal to 85
7. If an historic magnetic resonance imaging (MRI) is available, findings must exclude other causes of dementia.
8. Positive biomarker for brain amyloid pathology as indicated by assessment of at least one of the following:

   1. Current or historical CSF assessment with FDA-cleared assays, including Lumipulse® beta-amyloid ratio \[1-42/1-40\] ≤ 0.072, Elecsys® pTau 181/Aβ\[1-42\] greater than 0.023, Elecsys® tTau /Aβ\[1-42\] greater than 0.28, or other assays or cut-offs as they become FDA-cleared.
   2. Historical amyloid positron emission tomography (PET) assessment confirmed by the Sponsor or Designee.
9. Participants (or participant's legally authorized representative) and caregiver (s) who can sign an informed consent to participate in the study.
10. Participants who have one (or more) identified adult study partners (s) who, in the opinion of the Investigator, has sufficient contact with and knowledge about the participant as to be able to report knowledgably about the participant's cognition, function, behavior, and safety, and compliance with the protocol. The informant/care partner must be available by phone to provide information to the Investigator and study staff about the participant as well as agree to attend in-person clinic visits that require partner input for scale completion. The informant/care partner must be literate and provide informed consent and should be available for the duration of the study. The same informant/care partner is required to be consistent across all study visits except under rare, unavoidable circumstances (e.g., unexpected informant health crisis) that are approved by the Investigator and Sponsor.

Exclusion Criteria:

1. Participants who are female and are either pregnant, nursing, or of childbearing potential and not practicing effective contraception
2. Participants who have signs of significant delirium which, in the opinion of the Investigator, would interfere with this study
3. Participants who have any diagnosis of dementia or cognitive decline other than that related to AD, including, but not limited to concomitant history of significant head trauma, alcohol abuse, frontotemporal dementia, Huntington Disease, Parkinsonism (e.g., Parkinson's disease, Dementia with Lewy Bodies, etc.), significant cerebrovascular disease, and/or significant seizure disorder
4. Participants with any current psychiatric diagnosis if, in the judgment of the Investigator, the psychiatric disorder (e.g., schizophrenia) or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant's ability to complete the study
5. Participants with a history of vascular dementia
6. Participants with evidence of other neurological conditions thought to interfere with the evaluations in this study
7. Participants with a history of myocardial infarction, unstable angina, coronary artery disease, and/or New York Heart Association (NYHA) class III or IV heart failure within the last 12 months
8. Participants with uncontrolled hypertension (systolic blood pressure (BP) \>160 mmHg or diastolic BP \> 95 mmHg) or hypotension (systolic BP \<90 mmHg or diastolic BP \<50 mmHg). Participants may undergo repeated testing to ensure that accurate BP readings are obtained
9. Participants with a body mass index (BMI) \> 35 kg/m2
10. Participants with any of the following:

    1. elevation (\>2.5x upper limit of normal \[ULN\]) of AST (aspartate aminotransferase, ALT (alanine transaminase, or total bilirubin (unless known prior history of Gilbert's syndrome)
    2. deficiency (\< lower limit of normal \[LLN\]) of Vitamin B12
    3. known history of HIV (human immunodeficiency virus) positivity or positive test for HIV 1/2 at screening
    4. known history of Hepatitis C virus (HCV) or positive test for HCV antibody (HCVAb) at screening (unless negative on confirmatory PCR test)'
    5. positive test for Hepatitis B surface antigen (HBsAg)
    6. known history of neurosyphilis or positive test for RPR at screening
11. Participants who have history of cancer or malignant tumor within 5 years prior to screening with the exception of:

    1. Basal or squamous cell carcinoma of the skin or cervical dysplasia, which has been adequately treated
    2. In situ Grade 1 cervical cancer, fully treated at least 2 years prior to screening, and without recurrence.
    3. Prostate cancer, confined to the prostate gland, which has been adequately treated (e.g., surgery and/or radiation or watchful waiting) with normal or low and stable prostate-specific antigen (PSA) levels for 2 years prior to Screening
    4. Adequately treated non-metastatic breast cancer
12. Participants who in the opinion of the Investigator have an inadequately treated thyroid disorder
13. Participants with inherited degenerative retinal disease
14. Participants who have an undiagnosed or uncontrolled seizure disorder (and/or an epileptic syndrome), which has or could lead to cognitive impairment either from repeated seizures or the medications used to control the seizure disorder
15. Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol
16. Participants who have participated in any investigational drug or device trial within the previous 30 days or five half-lives of an investigational drug at Screening, whichever is longer
17. Participants taking an oral cholinesterase inhibitor and/or memantine not on a stable dose for at least 3 months prior to screening. Treatment and dosing should remain stable, with no changes throughout the trial.
18. Participants who have been and/or are currently being treated with anti-amyloid, anti-tau, or any other investigational therapies for AD
19. Participants who currently take any other PDE-5 Inhibitors (e.g., sildenafil)
20. Participants who are currently receiving (or unable to stop use for at least 14 days \[2 weeks\] prior to receiving the first dose of the AR1001 and throughout the study) prescription or nonprescription medications or other products known to be potent inhibitors of cytochrome P450 isozyme 3A4 (CYP3A4)
21. Alcohol or substance use disorder within the past 5 years according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
22. Participants who have previously participated in a clinical trial with AR1001
23. Participants, in the opinion of the Investigator, who are unsuitable to participate in the trial
24. Participants who in the opinion of the Investigator are at significant risk of suicide.
25. GDS-15 score greater than equal to 8 at Screening
26. Participants, in the opinion of the Investigator, who have any who have any contraindications to undergoing LP. Participants receiving ongoing anticoagulant therapy or antiplatelet therapy (other than aspirin and non-steroidal anti-inflammatory drugs \[NSAIDs\]) should also be excluded if it is considered unsafe to temporarily discontinue the therapy

Primary outcomes:
measure: Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)
timeFrame: 52 weeks
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog 13)
timeFrame: 52 weeks
measure: Amsterdam-Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV)
timeFrame: 52 weeks
measure: Geriatric Depression Scale (GDS)
timeFrame: 52 weeks
measure: Mini-Mental Status Examination (MMSE)
timeFrame: 52 weeks
Other outcomes:
measure: Safety Analysis
timeFrame: 156 weeks
measure: Biomarker Analysis
timeFrame: 156 weeks
measure: Exploratory Analysis
timeFrame: 156 weeks
Locations:
city: Phoenix
country: United States
facility: IMA Clinical Research Phoenix
state: Arizona
city: Scottsdale
country: United States
facility: Perseverance Research Center, LLC
state: Arizona
city: Scottsdale
country: United States
facility: Clinical Endpoints - N. Scottsdale
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Tempe
country: United States
facility: Voyage Medical
state: Arizona
city: Burlingame
country: United States
facility: Sutter Health's Palo Alto Medical Foundation
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Fullerton
country: United States
facility: Fullerton Neurology and Headache Center
state: California
city: Murrieta
country: United States
facility: Esperanza Clinical
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, INC
state: California
city: Pasadena
country: United States
facility: Havana Research Institute
state: California
city: San Diego
country: United States
facility: Kaizen Brain Center
state: California
city: San Jose
country: United States
facility: Adaptive Research
state: California
city: San Marcos
country: United States
facility: The Neuron Clinic
state: California
city: Stanford
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: Denver
country: United States
facility: Denver Neurological Research
state: Colorado
city: Denver
country: United States
facility: Mile High Research Center
state: Colorado
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research
state: Colorado
city: Apopka
country: United States
facility: Topaz Clinical Research
state: Florida
city: Clearwater
country: United States
facility: BayCare Health System, Inc
state: Florida
city: Clermont
country: United States
facility: Vertex Research Group
state: Florida
city: Daytona Beach
country: United States
facility: Arrow Clinical Trial
state: Florida
city: Loxahatchee Groves
country: United States
facility: Brainstorm Research - Loxahatchee
state: Florida
city: Maitland
country: United States
facility: ClinCloud LLC
state: Florida
city: Miami Gardens
country: United States
facility: Meridian International Research, Inc
state: Florida
city: Miami
country: United States
facility: Verus Clinical Research, Corp
state: Florida
city: Miami
country: United States
facility: Vitae Research Center, LLC
state: Florida
city: Miami
country: United States
facility: Caro Medcenter and Community Research
state: Florida
city: Miami
country: United States
facility: Allied Biomedical Research Institute, Inc
state: Florida
city: Miami
country: United States
facility: Future Life Clinical Trials
state: Florida
city: Miami
country: United States
facility: Brainstorm Research
state: Florida
city: Orlando
country: United States
facility: Charter Research - Orlando
state: Florida
city: Orlando
country: United States
facility: K2 Medical Research
state: Florida
city: Palm Beach
country: United States
facility: JEM Research Institute
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Angels Clinical Research Institute, Inc. - Tampa
state: Florida
city: The Villages
country: United States
facility: Charter Research - The Villages
state: Florida
city: Viera
country: United States
facility: ClinCloud, LLC Melbourn
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Atlanta
country: United States
facility: iResearch -Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Neuroscience Institute
state: Georgia
city: Decatur
country: United States
facility: Accel Research Sites
state: Georgia
city: Savannah
country: United States
facility: iResearch
state: Georgia
city: Chicago
country: United States
facility: Re:Cognition Health - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Tandem Clinical Research
state: Louisiana
city: New Bedford
country: United States
facility: BTC of New Bedford
state: Massachusetts
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Plymouth
country: United States
facility: Headlands Research - Eastern MA
state: Massachusetts
city: Waltham
country: United States
facility: Boston Paincare
state: Massachusetts
city: Ozark
country: United States
facility: Sharlin Health Neuroscience Research Center
state: Missouri
city: Lincoln
country: United States
facility: Alivation
state: Nebraska
city: Las Vegas
country: United States
facility: Wake Research- Clinical Research Center of Nevada, LLC
state: Nevada
city: Toms River
country: United States
facility: Advanced Memory Research Institute of New Jersey
state: New Jersey
city: Amherst
country: United States
facility: Dent Neuroscience Research Center
state: New York
city: New Windsor
country: United States
facility: Mid-Hudson Medical Research, PLLC - New Windsor
state: New York
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: Matthews
country: United States
facility: AMC Research, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Accellacare of Winston-Salem, Triad Neurological Associates
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center, LLC
state: Ohio
city: Dayton
country: United States
facility: American Clinical Research Institute, LLC
state: Ohio
city: East Providence
country: United States
facility: Rhode Island Mood and Memory REsearch
state: Rhode Island
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Knoxville
country: United States
facility: Center for Biomedical Research, LLC - Genesis Neuroscience Clinic
state: Tennessee
city: Beaumont
country: United States
facility: Gadolin Research LLC
state: Texas
city: Dallas
country: United States
facility: Kerwin Medical Center
state: Texas
city: Houston
country: United States
facility: Cognition Health Corporation- Texas
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network - Houston
state: Texas
city: Lubbock
country: United States
facility: Bhupesh Dihenia, MD, PA
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: Fairfax
country: United States
facility: Cognition Health Corporation
state: Virginia
city: Falls Church
country: United States
facility: Integrated Neurology Services
state: Virginia
city: Spokane
country: United States
facility: Kingfisher Cooperative
state: Washington
city: Crab Orchard
country: United States
facility: Vaught Neurological Services, PLLC
state: West Virginia
city: Wauwatosa
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
city: Rychnov Nad Kněžnou
country: Czechia
facility: Vestra Clinics
city: Gandrup
country: Denmark
facility: Sanos Clinic - Gandrup
city: Rennes
country: France
facility: CHU Rennes - Hopital Pontchaillou
city: Strasbourg
country: France
facility: CHRU de Strasbourg - Hopital de Hautepierre
city: Mannheim
country: Germany
facility: Institut fuer Studien zur Psychischen Gesundheit (ISPG)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Bundang-gu
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Dong-Gu
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Seoul Hospital
state: Gangseo-gu
city: Chuncheon
country: Korea, Republic of
facility: Hallym University Chuncheon Sacred Heart Hospital
state: Gangwon-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Namdong-Gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seodaemun-gu
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Guri-si
country: Korea, Republic of
facility: Hanyang University Guri Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Uijeongbu St. Mary's Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Chung ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Den Bosch
country: Netherlands
facility: Brain Research Center Den Bosch
city: Warszawa
country: Poland
facility: ETG Neurosciences Sp. Z.o.o.
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: AriBio Co., Ltd.
name: James Rock
role: STUDY_DIRECTOR
affiliation: Stanford University
name: Sharon Sha, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: