Ozanimod in Patients With Alzheimer's Disease

NCT06862960 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2024XHYG0025
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; Ozanimod; sphingosine-1-phosphate receptor; cognitive dysfunction

Outcome Measures

Primary Outcomes (2)

• Mean Absolute Change From Baseline in Brain Amyloid Plaque on 18F-florbetaben PET Scan on Ozanimod Group Versus Control Group

  18F-florbetaben PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a Centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.

  Baseline to Week 27

• Changes in serum GFAP

  We will quantify neuroinflammatory burden through plasma glial fibrillary acidic protein (GFAP) levels, comparing pre- and post-Ozanimod treatment, as well as between the Ozanimod group and the control group. Assessments will be conducted at baseline and week 27.

  Baseline to Week 27

Study Arms (2)

Ozanimod Group

EXPERIMENTAL

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.

Drug: Ozanimod

Control Group

ACTIVE COMPARATOR

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

Drug: Conventional medication

Interventions

Ozanimod DRUG

A sphingosine-1-phosphate receptor regulator

Ozanimod Group

Conventional medication DRUG

Conventional medications for moderate AD

Control Group

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The Clinical Dementia Rating-Sum of Boxes (CDR-SB) score must be between 9.5 and 15.5.
• Aged 55-80 years.
• Must be receiving treatment with stable doses of acetylcholinesterase inhibitors, memantine, or both for at least 3 months prior to the screening visit.
• 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.
• Have adequate literacy, vision, and hearing for neuropsychological testing in the opinion of the investigator at the time of screening.

You may not qualify if:

• 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.
• Contraindications to MRI (e.g., metal implants) or inability to tolerate/comply with the scanning procedure.
• Prior exposure to ozanimod or any other sphingosine-1-phosphate receptor regulators for AD before starting treatment with ozanimod subject of this study
• 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.
• 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.
• 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.
• Participants must not have a history of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

Sponsors & Collaborators

• ChenXiaoChun: lead
• Fujian Medical University Union Hospital: collaborator

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

ozanimod

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Central Study Contacts

Xiaochun Chen

CONTACT

＋86 139 0501 6998; chenxc998@mail.fjmu.edu.cn

Tianwen Huang

CONTACT

＋86 133 6591 7869; huangtianwen2002@mail.fjmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 5, 2025
• First Posted: March 7, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share