Assessing the Cognitive Benefits of Ozanimod and Their Brain-Biomarkers in MS

NCT06334094 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: IRB-23-486IM047-1054
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to investigate the cognitive benefits of ozanimod in individuals with Multiple Sclerosis (MS). The study aims to understand the neural basis of cognitive improvement in Relapsing-Remitting MS patients under ozanimod treatment using neuroimaging and behavioral techniques to characterize the brain and behavioral changes due to ozanimod treatment.

Conditions

Multiple Sclerosis

Keywords

Zeposia; Ozanimod

Outcome Measures

Primary Outcomes (1)

• Change in Processing Speed/Symbol-Digit Modality Test (SDMT) Performance

  SDMT is a neuropsychological assessment of processing speed in MS. The SDMT consists of 9 symbols that correspond to a number. Participants have 90 seconds to complete as many symbol to number associations as they can. Scoring is based on how many they can complete correctly in the span of 90 seconds. Therefore, to assess MS patients' cognitive changes while on ozanimod, MS patients' baseline performance to their performance following treatment on processing speed will be compared. The primary endpoint for this study will be a change from baseline in written SDMT performance of at least 4 points.

  1 year

Secondary Outcomes (5)

• Change in Volumetric Blood-Oxygen-Level-Dependent (BOLD) signal as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)

  1 year

• Change in Cerebral Blood Flow (CBF) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)

  1 year

• Change in Cerebral Metabolic Rate of Oxygen (CMRO2) as Measured by Dual Echo Functional Magnetic Resonance Imaging (fMRI)

  1 year

• Change in Whole Brain Volume as Measured By Structural Magnetic Resonance Imaging

  1 year

• Differences in Diffusion parameters of ozanimod-responders to non-responders as Measured By a Diffusion Kurtosis Resonance Imaging (DKI)

  1 year

Study Arms (1)

Ozanimod

EXPERIMENTAL

Participants will receive Ozanimod and work up to .92 mg. They will then take one pill daily for a duration of 12 months.

Drug: Ozanimod

Interventions

Ozanimod DRUG

A hard capsule that is taken daily for one year.

Also known as: Zeposia

Ozanimod

Eligibility Criteria

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

You may qualify if:

• English-speaking Relapsing-Remitting MS (RRMS; intermittent symptom exacerbations followed by periods of remission) patients.
• Male and female, between the ages of 18-55 years old will be recruited from the Texas Institute for Neurological Disorders (TIND) and MS Clinic of The University of Texas Southwestern. Study referrals will come from board-certified neurologists.
• Patients will have a McDonald-criteria diagnosis of RRMS, be \>30 days past exacerbation and corticosteroid treatment.
• Included patients will also be free of substance abuse and significant medical, other neurological, or psychiatric conditions unrelated to their MS disease course.
• Patient selection will be limited to patients that are treatment naïve (i.e., have not been previously treated for their MS) or require a change in treatment course.
• A clinical determination is needed as to whether ozanimod is the best treatment for a patient or whether a patient requires treatment change to ozanimod.
• All included participants will be right-handed and at least high-school educated.
• Only patients who score above 25 on the Telephone Interview for Cognitive Status (TICS) will be included.

You may not qualify if:

• During calibrated functional magnetic resonance imaging (fMRI) scanning, participants will inhale a carbon dioxide/room air solution to allow for calibration of BOLD signal. Thus, to ensure participant safety, the investigators exclude: smokers and those with MR-contraindicators, any participants with a history of respiratory or pulmonary problems (e.g., asthma, Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, tuberculosis), any participant with a history of cerebral vascular disease (e.g., cardiac disease, transient ischemic attack, migraines, stroke, arteriovenous malformation), any participant with a history of respiratory or pulmonary problems (e.g., asthma, Chronic Obstructive Pulmonary Disease (COPD), sarcoidosis, tuberculosis), and any participant with a history of cerebral vascular disease (e.g., cardiac disease, transient ischemic attack, migraines, stroke, arteriovenous malformation).
• Participants that present with EKG abnormalities consistent with FDA labeling contained within the ozanimod guidelines will be excluded as these abnormalities may be indication of dangerous negative side effects upon ozanimod consumption. EKG abnormalities include presence of atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block. Any experiences of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure within the last 6 months will exclude the patient. Contraindicators of ozanimod that may be found in the blood sample include presence of varicella titers and enzyme/protein levels that indicate liver dysfunction. Thus, these participants will be excluded.
• Patients who exhibit diseases other than MS that may be responsible for the patient's clinical, or MRI presentation will be excluded.
• Patients who exhibit a history of hypersensitivity to ozanimod or any drugs of similar chemical classes (i.e., sphingosine phosphates) will be excluded.
• Female participants who are pregnant or nursing will be excluded from the study. After the participant consents to being in the study, there will be a screening appointment to determine their eligibility, at which a pregnancy test will be provided. Other examinations, such as neurological assessments and EKGs, will occur at this appointment.
• Patients who are not native-English speakers will be excluded, as their English ability may limit their understanding of the instructions and performance on the neuropsychological tests.
• Patients who score below 25 on the Telephone Interview for Cognitive Status (TICS) will be excluded.

Sponsors & Collaborators

• The University of Texas at Dallas: lead
• Texas Institute for Neurological Disorders: collaborator

Study Sites (1)

Center for Brain Health

Dallas, Texas, 75228, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ozanimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bart Rypma, PhD

  The University of Texas at Dallas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 26, 2024
• First Posted: March 27, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: After one year; in perpetuity.
• Access Criteria: Bristol Myers Squibb (BMS) employment

Locations

US (1)