MIRODENAFIL DIHYDROCHLORIDE for Alzheimer's disease

Inclusion criteria

• {"criterion_text":"- 1. Male or female participants aged 55 to 85 years of age inclusive at the time of signing the informed consent form (ICF)\n- 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\n- 3. Participants with a history of subjective cognitive and memory decline with onset within 5 years before Screening, confirmed by study partner.\n- 4. Participants who have a MMSE score ≥ 20\n- 5. Participants with a CDR global rating of 0.5 or 1\n- 6. Participants with a Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score based on the Delayed Memory Index (DMI) score ≤ 85\n- 7. If an historic magnetic resonance imaging (MRI) is available, findings must exclude other causes of dementia\n- 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.\n- 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.\n- 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

• {"criterion_text":"- 1. Participants who are female and are either pregnant, nursing, or of childbearing potential and not practicing acceptable effective contraception\n- 2. Participants who have signs of significant ongoing delirium which may raise doubts about participant’s competence that would potentially interfere with study assessments\n- 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.\n- 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.\n- 5. Participants with a history of vascular dementia\n- 6. Participants with evidence of other neurological conditions thought to interfere with the evaluations in this study\n- 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\n- 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.\n- 9. Participants with a body mass index (BMI) ≥ 35 kg/m2\n- 10. Participants with any of the following: a.\tElevation (>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.\tDeficiency (< lower limit of normal [LLN]) of vitamin B12 c.\tKnown 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.\tKnown history of hepatitis C virus (HCV) or positive test for HCV antibody (HCV Ab) at screening unless negative on confirmatory PCR test e.\tPositive test for Hepatitis B surface antigen (HBsAg) f.\tKnown history of neurosyphilis or positive test for syphilis immunoglobulin G (IgG) at screening\n- 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.\n- 12. Participants who, in the opinion of the Investigator have an inadequately treated thyroid disorder.\n- 13. Participants with inherited degenerative retinal disease\n- 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.\n- 15. Participants who are being treated, or likely to require treatment during the study, with any medications prohibited by the study protocol\n- 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.\n- 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.\n- 18. Participants who have been and/or are currently being treated with anti-amyloid, anti-tau, or any investigational therapy for AD\n- 19. Participants who currently take any other PDE-5 inhibitors (e.g., sildenafil)\n- 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).\n- 21. Alcohol or substance use disorder within the past 5 years according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5)\n- 22. Participants who have previously participated in a clinical trial with AR1001\n- 23. Participants who, in the opinion of the Investigator, who are unsuitable to participate in the trial\n- 24. Participants who, in the opinion of the Investigator, are at significant risk of suicide\n- 25. GDS-15 score ≥8 at Screening\n- 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"}

Primary endpoints

• {"endpoint_text":"- 1. Change in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) from Baseline to Week 52","definition_or_measurement_approach":"Change from Baseline to Week 52 measured using the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)."}

Secondary endpoints

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

Methods

• Participant-facing printed materials (Brochure, Flyer, Participant Handbook) — multiple country-specific versions listed in documents.
• Digital outreach (Social Media Kit, BRC website text) — social media and website recruitment materials are present.
• Site/clinic outreach and presentations (BRC Presentation, Dear Doctor letter, GP letter) — materials addressed to healthcare professionals are listed.
• Participant journey and informational materials (Participant Journey, Participant Handbook) for prospective participants and caregivers.

Denmark

Earliest CTIS Part Ii Submission Date

12-04-2024

Latest Decision Or Authorization Date

29-05-2024

Processing Time Days

47

Number Of Participants

28

Poland

Earliest CTIS Part Ii Submission Date

12-08-2024

Latest Decision Or Authorization Date

16-09-2024

Processing Time Days

35

Number Of Participants

50

Netherlands

Earliest CTIS Part Ii Submission Date

11-04-2024

Latest Decision Or Authorization Date

29-05-2024

Processing Time Days

48

Number Of Participants

38

Czechia

Earliest CTIS Part Ii Submission Date

22-01-2024

Latest Decision Or Authorization Date

23-04-2024

Processing Time Days

92

Number Of Participants

76

Spain

Earliest CTIS Part Ii Submission Date

21-03-2024

Latest Decision Or Authorization Date

29-05-2024

Processing Time Days

69

Number Of Participants

102

Italy

Earliest CTIS Part Ii Submission Date

08-03-2024

Latest Decision Or Authorization Date

24-04-2024

Processing Time Days

47

Number Of Participants

68

Germany

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

29-05-2024

Processing Time Days

72

Number Of Participants

35

France

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

22-04-2024

Processing Time Days

34

Number Of Participants

82

Primary sponsor

Full Name

Aribio Co. Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Korea, Republic of

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Project/study management and other CRO functions (sponsorDuties codes 1,12,13,2,5 listed)

Name

Everest Clinical Research Corporation

Responsibilities

IP supply, pharmacovigilance and clinical operations (duties include Pharmacovigilance (Safety reporting) and supply responsibilities)

Name

WCG Clinical Inc.

Responsibilities

eCOA / scales support and other listed functions

Name

Labconnect LLC / LabConnect GmbH

Responsibilities

Laboratory/testing services

Name

Fisher Clinical Services GmbH

Responsibilities

Investigational Product Supply

Third parties

• {"country":"United States","full_name":"Kentucky Clinical Trials Laboratories LLC","duties_or_roles":"sponsorDuties codes: 4 (as listed in CTIS record)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Pentara Corp.","duties_or_roles":"Biostatistics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"Scales (eCOA); additional sponsorDuties codes: 6, 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"Multiple duties including Pharmacovigilance (Safety reporting) and IP supply/other (codes 10,11,15,3,6,7,8)","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"LabConnect GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Investigational Product Supply; other duties (codes 14, 15)","organisation_type":"Pharmaceutical company"}
• {"country":"Korea, Republic of","full_name":"Neurophet Inc.","duties_or_roles":"Imaging Central Reader (listed as value)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Multiple duties (codes 1,12,13,2,5) as listed","organisation_type":"Pharmaceutical company"}