Ozanimod in Patients With Alzheimer's Disease

ChenXiaoChun

Status and phase: Not yet enrolling; Phase 2

Conditions: Alzheimer Disease

Treatments: Drug: Ozanimod; Drug: Conventional medication

Study type: Interventional

Funder types: Other

Identifiers

NCT06862960

2024XHYG0025

Details and patient eligibility

About

The purpose of this study is to investigate the benefits of ozanimod in patients with moderate Alzheimer's disease.

Full description

This study will enroll 40 patients with moderate Alzheimer's disease (AD), who will be divided into two groups according to a fixed 1:1 (ozanimod : control) schedule. Patients in control group will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both), while those in the ozanimod group will receive the same approved AD treatment with the addition of ozanimod. The treatment will be for 27 weeks. All participants will undergo assessments at baseline and week 27, including 18F-florbetaben PET imaging, blood tests, and cognitive evaluations.

Enrollment: 40 estimated patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Must meet the 2024 diagnostic criteria for Alzheimer's disease (AD) published by the Alzheimer's Association (AA), and be in the moderate stage of AD.
2. The Clinical Dementia Rating-Sum of Boxes (CDR-SB) score must be between 9.5 and 15.5.
3. Aged 55-80 years.
4. Must be receiving treatment with stable doses of acetylcholinesterase inhibitors, memantine, or both for at least 3 months prior to the screening visit.
5. Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available by telephone at designated times.
6. Have adequate literacy, vision, and hearing for neuropsychological testing in the opinion of the investigator at the time of screening.

Exclusion criteria

1. Has diagnosis of a clinically relevant central nervous system (CNS) disease other than AD dementia or other condition that negatively impacts cognition or cognitive status chronically.

2. Contraindications to MRI (e.g., metal implants) or inability to tolerate/comply with the scanning procedure.

3. Prior exposure to ozanimod or any other sphingosine-1-phosphate receptor regulators for AD before starting treatment with ozanimod subject of this study

4. Participants must not have clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, renal, infectious diseases, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the participant at risk by participating in the study in the opinion of the Investigator.

5. Specific cardiac conditions are excluded, including history or presence of:

   i) Recent (within the past 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, New York Heart Association (NYHA) Class III/IV heart failure, or severe untreated sleep apnea.

   ii) Resting heart rate <55 beats per minute, second-degree (Mobitz type II) atrioventricular (AV) block, third-degree AV block, sick sinus syndrome, or sino-atrial block unless participants have a pacemaker in place.

   iii) Prolonged corrected QT interval by Fredericia's formula (QTcF; > 450 msec males and > 470 msec females), or participants at additional risk for QT prolongation.

6. Participants must not receive a live vaccine or a live-attenuated vaccine within 4 weeks prior to first dose or planning to receive a live vaccine or a live-attenuated vaccine during the study or within 90 days after discontinuation from study intervention.

7. Participants must not have a history of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Ozanimod Group

Experimental group

Description:

Patients will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both) plus ozanimod. Ozanimod will be administered in strict accordance with the stepwise dose-escalation protocol (Days 1-4: 0.23 mg/day; Days 5-7: 0.46 mg/day), followed by a maintenance dose of 0.92 mg once daily from Day 8. The total treatment duration will be 27 weeks, including both titration and maintenance phases.

Treatment:

Drug: Ozanimod

Control Group

Active Comparator group

Description:

Patients will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both).

Treatment:

Drug: Conventional medication