Efficacy and Safety of 26-Week Treatment of AR1001 in Patients With Mild to Moderate Alzheimer's Disease

NCT ID: NCT03625622

Last Updated: 2021-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2021-06-28

Brief Summary

A double-blinded, randomized, placebo-controlled study will be performed to evaluate the efficacy and safety of treating AR1001 in patients with mild to moderate Alzheimer's disease for 26 weeks.

Detailed Description

Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder in The United States affecting approximately 5.4 million Americans. AD is characterized by progressive loss in memory and as well as a decline in the ability to learn that is associated with neuronal death. Well known hallmarks of AD are neuritic plaques and neurofibrillary tangles and extensive inflammation. Currently, no treatment has been developed to fully cure or prevent the progression of dementia that is associated with AD.

AR1001 is a polypharmacological drug candidate being developed as a treatment for AD and shows great potential with favorable attributes for a central nervous system (CNS) drug (i.e., high specificity and potency, as well as good pharmacokinetic, bioavailability, CNS penetration, and ensured safety).

The clinical study of AR1001 aims to evaluate the efficacy and safety of AR1001 as a potential treatment for AD. Based on the preclinical results, AR1001 could be an effective treatment option with a mechanism of action that has not been explored for AD indication.

Conditions

Mild to Moderate Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo, orally administered once daily for 26 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo Oral Tablet

AR1001 - 10 mg

Active, AR1001 - 10 mg, orally administered once daily for 26 weeks.

Group Type: ACTIVE_COMPARATOR

AR1001

Intervention Type: DRUG

AR1001 Active Oral Tablet

AR1001 - 30 mg

Active, AR1001 - 30 mg, orally administered once daily for 26 weeks.

Group Type: ACTIVE_COMPARATOR

AR1001

Intervention Type: DRUG

AR1001 Active Oral Tablet

Interventions

AR1001

AR1001 Active Oral Tablet

Intervention Type: DRUG

Placebo

Placebo Oral Tablet

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female subjects aged 55-80 years at the time of signing the Informed Consent Form.

2. Subjects (or subject's legally acceptable representative) and caregiver(s) who can sign an Informed Consent to participate in the study. Same caregiver(s) must assist the subject throughout the entire duration of the study.

3. Subjects who have a diagnosis of probable Alzheimer's disease according to the NIA-AA (National Institute of Aging and Alzheimer's Associations, 2011) criteria with mild to moderate dementia (stage 4 - 5) at screening.

4. Subjects who have mild-to-moderate cognitive impairment with MMSE Score of 16-26 at screening.

5. Subjects who have an MRI (either 1.5T or 3T) or CT scan performed after onset of symptoms and prior to randomization with findings consistent with the diagnosis of dementia due to Alzheimer's disease and without any other clinically significant comorbid pathologies.

6. Subjects who have one (or more) identified adult study partner(s) who, in the opinion of the investigator, has sufficient contact with and knowledge about the subject as to be able to report knowledgeably about the subject's safety, compliance and adherence, cognition, function, and behavior.

Exclusion Criteria

1. Subjects who are female who are pregnant, nursing, or of childbearing potential and not practicing effective contraception.

2. Subjects who have signs of delirium.

3. Subjects who have had a cortical stroke within the preceding 2 years.

4. Subjects who have any diagnosis of dementia other than that related to Alzheimer's Disease, including concomitant vascular dementia.

5. Subjects who have a PET scan performed after onset of symptoms with negative amyloid results.

6. Subjects with a history of myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or IV heart failure or stroke within the last 12 months.

7. Subjects with uncontrolled hypertension (systolic blood pressure >160mm Hg or diastolic blood pressure > 95mm Hg) or hypotension (systolic blood pressure <90mm Hg or diastolic blood pressure <50mm Hg).

8. Subjects who have clinically significant renal impairment (creatinine > 1.5x ULN) or hepatic impairment (AST or ALT > 2.5x ULN or total bilirubin > 1.5x ULN).

9. Subjects 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.

10. Subjects who have history of untreated thyroid disorder or a seizure disorder.

11. Subjects who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol.

12. Subjects who have participated in any investigational drug or device trial within the previous 30 days or five half-lives of the investigational drug at screening, whichever one is longer.

13. Subjects who have any other clinically significant abnormal result in laboratory tests such as abnormally low B12 or high TSH levels, as determined by the Investigator.

14. Subjects with any current psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the subject's ability to complete the study.

15. Subjects whose treatment with FDA-approved AD medication (donepezil, galantamine, memantine, rivastigmine or their combinations) has not been stable for at least 3 months prior to screening. Treatment and dosing should remain stable, with no changes throughout the trial.

16. Subjects who are currently receiving (or unable to stop use for at least 21 days [3 weeks] prior to receiving the first dose of the AR1001 and throughout the study) prescription or non-prescription medications or other products known to be moderate or potent inhibitors/inducers of CYP3A4.

17. Subjects who have had any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the AR1001 and throughout the study.

18. Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study.

Extension Phase Continuation Criterion

1. Subjects enrolled in AR1001-ADP2-US01 and completed 26 weeks of assigned dosing.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AriBio Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Rock

Role: STUDY_DIRECTOR

SVP of global development

Locations

Advanced Clinical Research, Inc.

Banning, California, United States

Northern California Research

Sacramento, California, United States

Syrentis Clinical Research

Santa Ana, California, United States

Meridien Research

Lakeland, Florida, United States

Meridien - Maitland

Maitland, Florida, United States

The Neurology Research Group

Miami, Florida, United States

Accelerated Enrollment Solutions (AES)

Orlando, Florida, United States

IMIC, Inc

Palmetto Bay, Florida, United States

Meridien Research - Spring Hill

Spring Hill, Florida, United States

Meridien Research - St Petersburg

St. Petersburg, Florida, United States

Meridien Research - Tampa

Tampa, Florida, United States

NeuroStudies, LLC

Decatur, Georgia, United States

Advanced Clinical Research

Meridian, Idaho, United States

Wake Research - CRCNV

Las Vegas, Nevada, United States

Rapid Medical Research

Beachwood, Ohio, United States

Lynn Health Science Institute

Oklahoma City, Oklahoma, United States

Palmetto Clinical Research

Summerville, South Carolina, United States

Advanced Clinical Research - Cedar Park

Cedar Park, Texas, United States

FMC Science

Lampasas, Texas, United States

Advanced Clinical Research, Inc.

West Jordan, Utah, United States

Kingfisher Cooperative, LLC

Spokane, Washington, United States

Countries

United States

References

Greeley D, Nash M, Herskowitz B, Kim F, Rock J, Prins N, Kim S, Xi T, Busam JA, Tete B, Choung JJ, Sha SJ. A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhibitor, in patients with mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2025 Nov;12(9):100337. doi: 10.1016/j.tjpad.2025.100337. Epub 2025 Sep 5.

Reference Type: DERIVED

PMID: 40912996 (View on PubMed)

Other Identifiers

AR1001-ADP2-US01

Identifier Type: -

Identifier Source: org_study_id