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)
- Registration Number
- NCT05531526
- Lead Sponsor
- AriBio Co., Ltd.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1150
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Male or female participants aged 55 to 90 years of age inclusive at the time of signing the informed consent form
-
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
-
Participants with a history of subjective cognitive and memory decline with onset within 5 years before Screening, confirmed by study partner.
-
Participants who have a MMSE score greater than or equal to 20
-
Participants with a CDR global rating of 0.5 or 1
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Participants with a RBANS score based on the Delayed Memory Index (DMI) score less than or equal to 85
-
If an historic magnetic resonance imaging (MRI) is available, findings must exclude other causes of dementia.
-
Positive biomarker for brain amyloid pathology as indicated by assessment of at least one of the following:
- 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.
- Historical amyloid positron emission tomography (PET) assessment confirmed by the Sponsor or Designee.
-
Participants (or participant's legally authorized representative) and caregiver (s) who can sign an informed consent to participate in the study.
-
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.
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Participants who are female and are either pregnant, nursing, or of childbearing potential and not practicing effective contraception
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Participants who have signs of significant delirium which, in the opinion of the Investigator, would interfere with this study
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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
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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
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Participants with a history of vascular dementia
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Participants with evidence of other neurological conditions thought to interfere with the evaluations in this study
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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
-
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
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Participants with a body mass index (BMI) > 35 kg/m2
-
Participants with any of the following:
- 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)
- deficiency (< lower limit of normal [LLN]) of Vitamin B12
- known history of HIV (human immunodeficiency virus) positivity or positive test for HIV 1/2 at screening
- known history of Hepatitis C virus (HCV) or positive test for HCV antibody (HCVAb) at screening (unless negative on confirmatory PCR test)'
- positive test for Hepatitis B surface antigen (HBsAg)
- known history of neurosyphilis or positive test for RPR at screening
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Participants who have history of cancer or malignant tumor within 5 years prior to screening with the exception of:
- Basal or squamous cell carcinoma of the skin or cervical dysplasia, which has been adequately treated
- In situ Grade 1 cervical cancer, fully treated at least 2 years prior to screening, and without recurrence.
- 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
- Adequately treated non-metastatic breast cancer
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Participants who in the opinion of the Investigator have an inadequately treated thyroid disorder
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Participants with inherited degenerative retinal disease
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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
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Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol
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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
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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.
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Participants who have been and/or are currently being treated with anti-amyloid, anti-tau, or any other investigational therapies for AD
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Participants who currently take any other PDE-5 Inhibitors (e.g., sildenafil)
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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)
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Alcohol or substance use disorder within the past 5 years according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
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Participants who have previously participated in a clinical trial with AR1001
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Participants, in the opinion of the Investigator, who are unsuitable to participate in the trial
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Participants who in the opinion of the Investigator are at significant risk of suicide.
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GDS-15 score greater than equal to 8 at Screening
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B - Placebo Comparator Placebo Placebo QD will be administered daily for 52 weeks during the Treatment Phase of the study. In the Extension Phase, all eligible participants who choose to participate will receive AR1001 30 mg QD for 52 weeks. Group A - Active Comparator AR1001 Active, AR1001 30 mg QD will be administered daily for 52 weeks during the Treatment Phase of the study. In the Extension Phase, all eligible participants who choose to participate will receive AR1001 30 mg QD for 52 weeks.
- Primary Outcome Measures
Name Time Method Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) 52 weeks Change in the CDR-SB from Baseline to Week 52
- Secondary Outcome Measures
Name Time Method Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog 13) 52 weeks Change in ADAS-Cog 13 from Baseline to Week 52
Amsterdam-Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV) 52 weeks Change in the A-IADL-Q-SV from Baseline to Week 52
Mini-Mental Status Examination (MMSE) 52 weeks Change in the MMSE from Baseline to Week 52
Geriatric Depression Scale (GDS) 52 weeks Change in the GDS from Baseline to Week 52
Trial Locations
- Locations (102)
Kingfisher Cooperative
🇺🇸Spokane, Washington, United States
Vaught Neurological Services, PLLC
🇺🇸Crab Orchard, West Virginia, United States
Medical College of Wisconsin
🇺🇸Wauwatosa, Wisconsin, United States
Xuanwu Hospital Capital Medical University
🇨🇳Beijing, China
Vestra Clinics
🇨🇿Rychnov Nad Kněžnou, Czechia
Sanos Clinic - Gandrup
🇩🇰Gandrup, Denmark
CHU Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
CHRU de Strasbourg - Hopital de Hautepierre
🇫🇷Strasbourg, France
Institut fuer Studien zur Psychischen Gesundheit (ISPG)
🇩🇪Mannheim, Germany
IMA Clinical Research Phoenix
🇺🇸Phoenix, Arizona, United States
Havana Research Institute
🇺🇸Pasadena, California, United States
Kaizen Brain Center
🇺🇸San Diego, California, United States
Adaptive Research
🇺🇸San Jose, California, United States
The Neuron Clinic
🇺🇸San Marcos, California, United States
Stanford Neuroscience Health Center
🇺🇸Stanford, California, United States
Denver Neurological Research
🇺🇸Denver, Colorado, United States
Mile High Research Center
🇺🇸Denver, Colorado, United States
CenExel Rocky Mountain Clinical Research
🇺🇸Englewood, Colorado, United States
Topaz Clinical Research
🇺🇸Apopka, Florida, United States
BayCare Health System, Inc
🇺🇸Clearwater, Florida, United States
Vertex Research Group
🇺🇸Clermont, Florida, United States
Arrow Clinical Trial
🇺🇸Daytona Beach, Florida, United States
Brainstorm Research - Loxahatchee
🇺🇸Loxahatchee Groves, Florida, United States
ClinCloud LLC
🇺🇸Maitland, Florida, United States
Meridian International Research, Inc
🇺🇸Miami Gardens, Florida, United States
Verus Clinical Research, Corp
🇺🇸Miami, Florida, United States
Vitae Research Center, LLC
🇺🇸Miami, Florida, United States
Caro Medcenter and Community Research
🇺🇸Miami, Florida, United States
Allied Biomedical Research Institute, Inc
🇺🇸Miami, Florida, United States
Future Life Clinical Trials
🇺🇸Miami, Florida, United States
Brainstorm Research
🇺🇸Miami, Florida, United States
Charter Research - Orlando
🇺🇸Orlando, Florida, United States
K2 Medical Research
🇺🇸Orlando, Florida, United States
JEM Research Institute
🇺🇸Palm Beach, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Angels Clinical Research Institute, Inc. - Tampa
🇺🇸Tampa, Florida, United States
Charter Research - The Villages
🇺🇸The Villages, Florida, United States
ClinCloud, LLC Melbourn
🇺🇸Viera, Florida, United States
Conquest Research
🇺🇸Winter Park, Florida, United States
iResearch -Atlanta
🇺🇸Atlanta, Georgia, United States
Atlanta Neuroscience Institute
🇺🇸Atlanta, Georgia, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
Headlands Research - Eastern MA
🇺🇸Plymouth, Massachusetts, United States
Boston Paincare
🇺🇸Waltham, Massachusetts, United States
Sharlin Health Neuroscience Research Center
🇺🇸Ozark, Missouri, United States
Alivation
🇺🇸Lincoln, Nebraska, United States
Wake Research- Clinical Research Center of Nevada, LLC
🇺🇸Las Vegas, Nevada, United States
Advanced Memory Research Institute of New Jersey
🇺🇸Toms River, New Jersey, United States
Dent Neuroscience Research Center
🇺🇸Amherst, New York, United States
Mid-Hudson Medical Research, PLLC - New Windsor
🇺🇸New Windsor, New York, United States
Triad Clinical Trials
🇺🇸Greensboro, North Carolina, United States
AMC Research, LLC
🇺🇸Matthews, North Carolina, United States
Rhode Island Mood and Memory REsearch
🇺🇸East Providence, Rhode Island, United States
Health Concepts
🇺🇸Rapid City, South Dakota, United States
Neurology Clinic, P.C.
🇺🇸Cordova, Tennessee, United States
Center for Biomedical Research, LLC - Genesis Neuroscience Clinic
🇺🇸Knoxville, Tennessee, United States
Gadolin Research LLC
🇺🇸Beaumont, Texas, United States
Kerwin Medical Center
🇺🇸Dallas, Texas, United States
Cognition Health Corporation- Texas
🇺🇸Houston, Texas, United States
Clinical Trial Network - Houston
🇺🇸Houston, Texas, United States
Bhupesh Dihenia, MD, PA
🇺🇸Lubbock, Texas, United States
Wasatch Clinical Research, LLC
🇺🇸Salt Lake City, Utah, United States
Cognition Health Corporation
🇺🇸Fairfax, Virginia, United States
Integrated Neurology Services
🇺🇸Falls Church, Virginia, United States
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Bundang-gu, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Dong-Gu, Korea, Republic of
Ewha Womans University Seoul Hospital
🇰🇷Seoul, Gangseo-gu, Korea, Republic of
Hallym University Chuncheon Sacred Heart Hospital
🇰🇷Chuncheon, Gangwon-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Namdong-Gu, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Hanyang University Guri Hospital
🇰🇷Guri-si, Korea, Republic of
Uijeongbu St. Mary's Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St.Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Chung ang University Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Brain Research Center Den Bosch
🇳🇱Den Bosch, Netherlands
ETG Neurosciences Sp. Z.o.o.
🇵🇱Warszawa, Poland
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hammersmith Hospital
🇬🇧London, United Kingdom
Perseverance Research Center, LLC
🇺🇸Scottsdale, Arizona, United States
Clinical Endpoints - N. Scottsdale
🇺🇸Scottsdale, Arizona, United States
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Voyage Medical
🇺🇸Tempe, Arizona, United States
Sutter Health's Palo Alto Medical Foundation
🇺🇸Burlingame, California, United States
Neuro-Pain Medical Center
🇺🇸Fresno, California, United States
Fullerton Neurology and Headache Center
🇺🇸Fullerton, California, United States
Esperanza Clinical
🇺🇸Murrieta, California, United States
Valley Clinical Trials, INC
🇺🇸Northridge, California, United States
Accel Research Sites
🇺🇸Decatur, Georgia, United States
iResearch
🇺🇸Savannah, Georgia, United States
Re:Cognition Health - Chicago
🇺🇸Chicago, Illinois, United States
Tandem Clinical Research
🇺🇸New Orleans, Louisiana, United States
BTC of New Bedford
🇺🇸New Bedford, Massachusetts, United States
Accellacare of Winston-Salem, Triad Neurological Associates
🇺🇸Winston-Salem, North Carolina, United States
NeuroScience Research Center, LLC
🇺🇸Canton, Ohio, United States
American Clinical Research Institute, LLC
🇺🇸Dayton, Ohio, United States