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)

Alzheimer Disease Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05531526
• Other study ID #: AR1001-ADP3-US01
• Status: Recruiting
• Phase: Phase 3
• Start date: December 23, 2022
• Est. completion date: December 2027

Study information

• Verified date: June 2024
• Source: AriBio Co., Ltd.
• Contact: Phil Kang
• Phone: 858-412-5467
• Email: Polaris-ad[@]aribiousa.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1150
• Est. completion date: December 2027
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

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/Aß[1-42] greater than 0.023, Elecsys® tTau /Aß[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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• AR1001
AR1001 Active Oral Tablet
• Placebo
Placebo Oral Tablet

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Chuncheon Sacred Heart Hospital	Chuncheon	Gangwon-do
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Hanyang University Guri Hospital	Guri-si
Korea, Republic of	Chonnam National University Hospital	Gwangju	Dong-Gu
Korea, Republic of	Uijeongbu St. Mary's Hospital	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Namdong-Gu
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Bundang-gu
Korea, Republic of	Chung ang University Hospital	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Ewha Womans University Seoul Hospital	Seoul	Gangseo-gu
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seodaemun-gu
Korea, Republic of	The Catholic University of Korea Seoul St.Mary's Hospital	Seoul
United Kingdom	Hammersmith Hospital	London
United States	Dent Neuroscience Research Center	Amherst	New York
United States	Topaz Clinical Research	Apopka	Florida
United States	Atlanta Neuroscience Institute	Atlanta	Georgia
United States	iResearch -Atlanta	Atlanta	Georgia
United States	NeuroScience Research Center, LLC	Canton	Ohio
United States	Re:Cognition Health - Chicago	Chicago	Illinois
United States	BayCare Health System, Inc	Clearwater	Florida
United States	Vertex Research Group	Clermont	Florida
United States	Neurology Clinic, P.C.	Cordova	Tennessee
United States	Vaught Neurological Services, PLLC	Crab Orchard	West Virginia
United States	Kerwin Medical Center	Dallas	Texas
United States	American Clinical Research Institute, LLC	Dayton	Ohio
United States	Arrow Clinical Trial	Daytona Beach	Florida
United States	Accel Research Sites	Decatur	Georgia
United States	Denver Neurological Research	Denver	Colorado
United States	Mile High Research Center	Denver	Colorado
United States	Rhode Island Mood and Memory REsearch	East Providence	Rhode Island
United States	Cognition Health Corporation	Fairfax	Virginia
United States	Integrated Neurology Services	Falls Church	Virginia
United States	Neuro-Pain Medical Center	Fresno	California
United States	Triad Clinical Trials	Greensboro	North Carolina
United States	Clinical Trial Network - Houston	Houston	Texas
United States	Cognition Health Corporation- Texas	Houston	Texas
United States	Center for Biomedical Research, LLC - Genesis Neuroscience Clinic	Knoxville	Tennessee
United States	Charter Research - Lady Lake	Lady Lake	Florida
United States	Wake Research- Clinical Research Center of Nevada, LLC	Las Vegas	Nevada
United States	Alivation	Lincoln	Nebraska
United States	Brainstorm Research - Loxahatchee	Loxahatchee Groves	Florida
United States	Bhupesh Dihenia, MD, PA	Lubbock	Texas
United States	ClinCloud LLC	Maitland	Florida
United States	AMC Research, LLC	Matthews	North Carolina
United States	Allied Biomedical Research Institute, Inc	Miami	Florida
United States	Brainstorm Research	Miami	Florida
United States	Caro Medcenter and Community Research	Miami	Florida
United States	Future Life Clinical Trials	Miami	Florida
United States	Verus Clinical Research, Corp	Miami	Florida
United States	Vitae Research Center, LLC	Miami	Florida
United States	Meridian International Research, Inc	Miami Gardens	Florida
United States	BTC of New Bedford	New Bedford	Massachusetts
United States	Tandem Clinical Research	New Orleans	Louisiana
United States	Mid-Hudson Medical Research, PLLC - New Windsor	New Windsor	New York
United States	Boston Center for Memory	Newton	Massachusetts
United States	Valley Clinical Trials, INC	Northridge	California
United States	K2 Medical Research	Orlando	Florida
United States	Sharlin Health Neuroscience Research Center	Ozark	Missouri
United States	JEM Research Institute	Palm Beach	Florida
United States	Havana Research Institute	Pasadena	California
United States	IMA Clinical Research Phoenix	Phoenix	Arizona
United States	Headlands Research - Eastern MA	Plymouth	Massachusetts
United States	Progressive Medical Research	Port Orange	Florida
United States	Health Concepts	Rapid City	South Dakota
United States	Sutter Health's Palo Alto Medical Foundation	Sacramento	California
United States	Wasatch Clinical Research, LLC	Salt Lake City	Utah
United States	Kaizen Brain Center	San Diego	California
United States	Adaptive Research	San Jose	California
United States	iResearch	Savannah	Georgia
United States	Perseverance Research Center, LLC	Scottsdale	Arizona
United States	Kingfisher Cooperative	Spokane	Washington
United States	Angels Clinical Research Institute, Inc. - Tampa	Tampa	Florida
United States	The Neuron CLinic	Temecula	California
United States	Voyage Medical	Tempe	Arizona
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	ClinCloud, LLC Melbourn	Viera	Florida
United States	Boston Paincare	Waltham	Massachusetts
United States	Accellacare of Winston-Salem, Triad Neurological Associates	Winston-Salem	North Carolina
United States	Charter Research - Winter Park	Winter Park	Florida
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AriBio Co., Ltd.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Analysis	Frequency of treatment emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs); Changes in C-SSRS (Columbia Suicide Severity Rating Scale)	156 weeks
Other	Biomarker Analysis	Change in plasma/CSF biomarker levels from Baseline to Week 52 and the end of the Extension Phase.	156 weeks
Other	Exploratory Analysis	Change in both primary and secondary endpoints from Baseline and Week 52 to the end of the extension study.	156 weeks
Primary	Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)	Change in the CDR-SB from Baseline to Week 52	52 weeks
Secondary	Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog 13)	Change in ADAS-Cog 13 from Baseline to Week 52	52 weeks
Secondary	Amsterdam-Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV)	Change in the A-IADL-Q-SV from Baseline to Week 52	52 weeks
Secondary	Geriatric Depression Scale (GDS)	Change in the GDS from Baseline to Week 52	52 weeks
Secondary	Mini-Mental Status Examination (MMSE)	Change in the MMSE from Baseline to Week 52	52 weeks