A Phase 3 Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy and Safety of AR1001 in Participants with Early Alzheimer’s Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aribio Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

26 Jun 2024 → ongoing

Decision date (initial)

2024-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Aribio Co., Ltd.

External identifiers

EU CT number

2023-508306-15-00

WHO UTN

U1111-1298-0156

ClinicalTrials.gov

NCT05531526

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

1. To evaluate the efficacy of AR1001 compared with Placebo in participants with early AD

Secondary objectives 1

1. 1. To further evaluate the efficacy of AR1001 compared with Placebo in participants with early AD

Conditions and MedDRA coding

Alzheimer’s Disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Male or female participants aged 55 to 85 years of age inclusive at the time of signing the informed consent form (ICF)
2. 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. 3. Participants with a history of subjective cognitive and memory decline with onset within 5 years before Screening, confirmed by study partner.
4. 4. Participants who have a MMSE score ≥ 20
5. 5. Participants with a CDR global rating of 0.5 or 1
6. 6. Participants with a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score based on the Delayed Memory Index (DMI) score ≤ 85
7. 7. If an historic magnetic resonance imaging (MRI) is available, findings must exclude other causes of dementia
8. 8. Positive biomarker for brain amyloid pathology as indicated by assessment of at least one of the following: a. Current or historical CSF assessment with FDA-cleared and/or CE-marked assays (e.g., Lumipulse® Aβ ratio [1-42/1-40] ≤ 0.072, Elecsys® p-tau 181/Aβ[1-42] > 0.023, Elecsys® total Tau/Aβ[1-42] > 0.28. b. Historical amyloid positron emission tomography (PET) assessment with FDA-cleared and/or CE-marked tracer for AD diagnosis, confirmed by the Sponsor or central read.
9. 9. Participants and caregiver(s) who can sign an informed consent to participate in the study. Participants are expected to have the capacity to consent to study participation. Investigators will assess and confirm participants’ capacity to consent/assent.
10. 10. Participants who have 1 (or more) identified adult study partner(s) who, in the opinion of the Investigator, has a personal contact of a minimum of 5 days a week with the participant and are able to report knowledgably about the participant’s cognition, function, behavior, 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 able to understand the requirements of participation 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 26

1. 1. Participants who are female and are either pregnant, nursing, or of childbearing potential and not practicing acceptable effective contraception
2. 2. Participants who have signs of significant ongoing delirium which may raise doubts about participant’s competence that would potentially interfere with study assessments
3. 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. 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. 5. Participants with a history of vascular dementia
6. 6. Participants with evidence of other neurological conditions thought to interfere with the evaluations in this study
7. 7. Participants with a history of myocardial infarction, unstable angina, significant coronary artery disease, and/or New York Heart Association (NYHA) class III or IV heart failure within the last 12 months
8. 8. Participants with uncontrolled hypertension (e.g., systolic blood pressure (BP) >160 mmHg or diastolic BP > 95 mmHg) or hypotension (e.g., systolic BP <90 mmHg or diastolic BP <50 mmHg). Participants may undergo repeated testing to ensure that accurate BP readings are obtained.
9. 9. Participants with a body mass index (BMI) ≥ 35 kg/m2
10. 10. Participants with any of the following: a. Elevation (>2.5× upper limit of normal [ULN]) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin (unless known prior history of Gilbert’s syndrome). b. Deficiency (< lower limit of normal [LLN]) of vitamin B12 c. Known history of human immunodeficiency virus (HIV) positivity or positive test for HIV 1/2 at screening unless negative on confirmatory polymerase chain reaction (PCR) d. Known history of hepatitis C virus (HCV) or positive test for HCV antibody (HCV Ab) at screening unless negative on confirmatory PCR test e. Positive test for Hepatitis B surface antigen (HBsAg) f. Known history of neurosyphilis or positive test for syphilis immunoglobulin G (IgG) at screening
11. 11. Participants who have history of cancer or malignant tumor within 5 years prior to screening with the exception of: a. Basal or squamous cell carcinoma of the skin or cervical dysplasia, which has been adequately treated. b. In situ Grade 1 cervical cancer, fully treated at least 2 years prior to screening, and without recurrence. c. 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. d. Adequately treated non-metastatic breast cancer.
12. 12. Participants who, in the opinion of the Investigator have an inadequately treated thyroid disorder.
13. 13. Participants with inherited degenerative retinal disease
14. 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. 15. Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol
16. 16. Participants who have participated in any investigational drug or device trial within the previous 30 days or 5 half-lives of an investigational drug at Screening, whichever is longer.
17. 17. Participants taking a 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. 18. Participants who have been and/or are currently being treated with anti-amyloid, anti-tau, or any investigational therapy for AD
19. 19. Participants who currently take any other PDE-5 inhibitors (e.g., sildenafil)
20. 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 or inducers of cytochrome P450 isozyme 3A4 (CYP3A4).
21. 21. Alcohol or substance use disorder within the past 5 years according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
22. 22. Participants who have previously participated in a clinical trial with AR1001
23. 23. Participants who, in the opinion of the Investigator, who are unsuitable to participate in the trial
24. 24. Participants who, in the opinion of the Investigator, are at significant risk of suicide
25. 25. GDS-15 score ≥8 at Screening
26. 26. Participants requiring a lumbar puncture (LP) to verify amyloid pathology who have a contraindication to undergoing LP in the opinion of the Investigator. Participants requiring LP who are 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 or contraindicated to temporarily discontinue the therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Change in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) from Baseline to Week 52

Secondary endpoints 4

1. 1. Change in the Alzheimer’s Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog 13) from Baseline to Week 52
2. 2. Change in the Amsterdam-Instrumental Activities of Daily Living Questionnaire-Short Version (A-IADL-Q-SV) from Baseline to Week 52
3. 3. Change in the Geriatric Depression Scale-15 (GDS-15) from Baseline to Week 52
4. 4. Change in the Mini-Mental Status Examination (MMSE) from Baseline to Week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aribio Co. Ltd.

Sponsor organisation

Aribio Co. Ltd.

Address

56 Dongpangyo-Ro, Bundang-Gu Bundang-Gu

City

Seongnam-Si

Postcode

13535

Country

Korea, Republic of

Scientific contact point

Organisation

Aribio Co. Ltd.

Contact name

James Rock

Public contact point

Organisation

Aribio Co. Ltd.

Contact name

Fred Kim

Third parties 9

Locations

8 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 161 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

19 submissions — initial application plus substantial / non-substantial modifications