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)

• ClinicalTrials.gov Identifier: NCT05531526
• Recruitment Status: Recruiting
• First Posted: September 8, 2022
• Last Update Posted: May 30, 2023
• Sponsor: AriBio Co., Ltd.
• Information provided by (Responsible Party): AriBio Co., Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: AR1001; Drug: Placebo	Phase 3

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.

AriBio completed a Phase 2 study in the United States (US) with AR1001 for the treatment of participants with mild to moderate AD. After confirming AR1001's therapeutic benefit in the mild AD population, AriBio is proceeding with a Phase 3 program in an early AD population including participants with MCI and mild dementia.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 800 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: double-blind, randomized, placebo-controlled
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 23, 2022
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2027

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group A - Active Comparator; 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 104 weeks.	Drug: AR1001; AR1001 Active Oral Tablet
Placebo Comparator: Group B - Placebo Comparator; 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 104 weeks.	Drug: Placebo; Placebo Oral Tablet

Outcome Measures

Primary Outcome Measures :

1. Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) [ Time Frame: 52 weeks ]
   Change in the CDR-SB from Baseline to Week 52

Secondary Outcome Measures :

1. Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog 13) [ Time Frame: 52 weeks ]
   Change in ADAS-Cog 13 from Baseline to Week 52
2. Amsterdam-Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV) [ Time Frame: 52 weeks ]
   Change in the A-IADL-Q-SV from Baseline to Week 52
3. Geriatric Depression Scale (GDS) [ Time Frame: 52 weeks ]
   Change in the GDS from Baseline to Week 52
4. Mini-Mental Status Examination (MMSE) [ Time Frame: 52 weeks ]
   Change in the MMSE from Baseline to Week 52
5. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: 52 weeks ]
   Change in the RBANS from Baseline to Week 52

Other Outcome Measures:

1. Safety Analysis [ Time Frame: 156 weeks ]
   • Frequency of treatment emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
   • Changes in C-SSRS (Columbia Suicide Severity Rating Scale)
2. Biomarker Analysis [ Time Frame: 156 weeks ]
   Change in plasma/CSF biomarker levels from Baseline to Week 52 and the end of the Extension Phase.
3. Exploratory Analysis [ Time Frame: 156 weeks ]
   Change in both primary and secondary endpoints from Baseline and Week 52 to the end of the extension study.

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female participants aged 55 to 80 years of age 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 NIA AA at Screening
3. Participants with a history of subjective cognitive and memory decline with onset within 3 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 less than or equal to 85 based on the Delayed Memory Index (DMI) score
7. Participants who have had a magnetic resonance imaging (MRI) or computer tomography (CT) scan performed after onset of symptoms and within 2 years prior to screening with findings consistent with the diagnosis of AD and without any other clinically significant comorbid pathologies
8. Confirmed amyloid beta pathology by cerebrospinal fluid (CSF) analysis

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 delirium
3. Participants who have any diagnosis of dementia or cognitive decline other than that related to Alzheimer's disease, including, but not limited to concomitant history of significant head trauma, alcohol abuse, frontotemporal dementia, Huntington Disease, and Parkinsonism (e.g., Parkinson's disease, Dementia with Lewy Bodies, etc.)
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 vascular dementia and/or a Hachinski Ischemic Scale (HIS) score ≥7
6. Participants with a recent MRI with evidence of central nervous system (CNS) infection, cerebrovascular (CBV) disease, or other neurological disease thought to interfere with the evaluations in this study
7. Participants with a history of myocardial infarction, unstable angina, coronary artery disease, 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 >160 mmHg or diastolic blood pressure > 95 mmHg) or hypotension (systolic blood pressure <90 mmHg or diastolic blood pressure <50 mmHg). Participants may undergo repeated testing to ensure that accurate blood pressure readings are obtained
9. Participants with a body mass index (BMI) > 35 kg/m2
10. Participants who have any other clinically significant abnormal laboratory tests such as elevated aspartate aminotransferase (AST), alanine transaminase (ALT), or total bilirubin levels, or abnormally low vitamin B12, high TSH levels, or evidence of folic acid deficiency, as determined by the Investigator

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 (surgery and/or radiation) with normal or low and stable PSA levels for 2 years prior to Screening
    4. Adequately treated non-metastatic breast cancer
12. Participants who have history of untreated 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

Contacts and Locations

Contacts

Contact: John Kim; 858-412-5467; jkim@aribiousa.com

Locations

United States, Arizona

Perseverance Research Center, LLC; Recruiting

Scottsdale, Arizona, United States, 85254

Contact: Brandon McCravey

United States, Colorado

Mile High Research Center; Recruiting

Denver, Colorado, United States, 80218

Contact: Amy Greaves

United States, Florida

Arrow Clinical Trial; Recruiting

Daytona Beach, Florida, United States, 32117

Contact: Vishnu Nitta

Venus Clinical Research, Corp; Recruiting

Miami, Florida, United States, 33134

Contact: Jose Noel delgado

Brainstorm Research; Recruiting

Miami, Florida, United States, 33176

Contact: Savannah Rodriguez

Conquest Research; Recruiting

Winter Park, Florida, United States, 32789

Contact: Kendra Tandeski

United States, Georgia

Accel Research Sites; Recruiting

Decatur, Georgia, United States, 30030

Contact: Jennifer Scantlin

United States, Massachusetts

Boston Paincare; Recruiting

Waltham, Massachusetts, United States, 02451

Contact: Jessica O'Brien

United States, Washington

Kingfisher Cooperative; Recruiting

Spokane, Washington, United States, 99202

Contact: Nichole Godsey

Sponsors and Collaborators

AriBio Co., Ltd.

Investigators

• Study Director: Fred Kim; AriBio Co., Ltd.

More Information

• Responsible Party: AriBio Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05531526
• Other Study ID Numbers: AR1001-ADP3-US01
• First Posted: September 8, 2022
• Last Update Posted: May 30, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AriBio Co., Ltd.:

AR1001; AD; Early AD

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders