Clinical trial NCT06862960: Ozanimod in Patients with Alzheimer's Disease
Official title: Ozanimod for the Treatment of Alzheimer's Disease: a Proof-of-concept Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Ozanimod
sphingosine-1-phosphate receptor
cognitive dysfunction
Lead sponsor: Fujian Medical University Union Hospital
Sponsor class: OTHER
Collaborators: name: Fujian Medical University Union Hospital
First posted: 2025-03-07
Enrollment: 40
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: Inclusion Criteria:

1. The participants are moderate AD patients who meet the diagnostic criteria for AD proposed by the National Institute on Aging and the Alzheimer's Association (NIA-AA) in 2023 and have a disease course of more than 6 months.
2. Mini-Mental State Examination (MMSE) score of 12-20 or Clinical Dementia Rating (CDR) global score of 2 (inclusive).
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 28 days after discontinuation from study intervention.
7. Participants must not have a history of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

Primary outcomes:
measure: Mean Absolute Change From Baseline in Brain Amyloid Plaque on 18F-florbetaben PET Scan on Ozanimod Group Versus Control Group
timeFrame: Baseline to Week 27
measure: Changes in serum GFAP
timeFrame: Baseline to Week 27
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: