A Phase 3 Study of the Efficacy and Safety of AR1001 in Participants With Early AD

• Status: Not yet recruiting
• Trial end date: 2027-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AriBio Co., Ltd.

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. Participants (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. Participants who have a diagnosis of early Alzheimer's disease (AD)

1. Mild cognitive impairment or mild dementia defined by stages 3 - 4 according to the NIA-AA (National Institute of Aging and Alzheimer's Associations, 2018) at screening and baseline [3].

2. Confirmed amyloid beta pathology by cerebrospinal fluid (CSF) analysis with beta-amyloid ratio (1-42/1-40) of 0.058 or lower.

4. Participants who have RCFT Score less than or equal to 31 at screening.

5. Participants who have MMSE Score greater than or equal to 20 at screening.

6. Participants with a CDR global rating score of:

1. 0.5 with a score of 0.5 or more in at least three of the five domains other than memory or;

2. 1

7. Participants who have an MRI or 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. Participants 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 knowledgably about the subject's safety, compliance and adherence, cognition, function, and behavior.

9. Subject and/or the subject's legally authorized representative and the subject's study partner able and willing to sign an ICF prior to beginning any study procedures including consent for genotyping for apolipoprotein E4 allele.

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 head trauma, alcohol abuse, frontotemporal dementia, Huntington Disease, Parkinson's disease, Dementia with Lewy Bodies and/or Parkinsonism.

4. Participants with any current psychiatric diagnosis 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 (e.g., schizophrenia).

5. Participants with vascular dementia and/or 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 evaluation in this study.

7. Participants with a history of myocardial infarction, unstable angina, coronary artery disease, New York Heart Association (NYHA) class III or IV heart failure within the last 12 months.

8. Participants 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). Participants should undergo repeating testing to ensure accurate blood pressure readings are obtained.

9. Participants with BMI > 35

10. Participants who have any other clinically significant abnormal result in laboratory tests such as elevated AST, ALT or total bilirubin levels, abnormally low B12 or 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 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.

14. Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol (Appendix 1).

15. Participants 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.

16. Participants whose treatment with FDA-approved AD medication (donepezil, galantamine, rivastigmine or their combinations) has not been stable for at least 6 months prior to screening. Treatment and dosing should remain stable, with no changes throughout the trial.

17. Participants who have been and/or are currently being treated with memantine, anti-amyloid, anti-tau, or other investigational therapies for AD.

18. Participants who currently take any other phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil).

19. Alcohol or substance use disorder within the past 5 years according to DSM-5.

20. Participants 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.

21. Participants who have previously participated in a clinical trial with AR1001.

22. Participants, in the opinion of the Investigator, who are unsuitable to participate in the study.

23. Geriatric Depression Scale (GDS) score >=8 at Screening.