Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod

NCT06529406 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 23-1686
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

A multi-center pilot study to evaluate safety and efficacy of ozanimod as de-escalation therapy in clinically stable MS patients previously treated with anti-CD20 therapy.

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• New T2 lesions count

  Number of new T2 lesions on MRI scans.

  36 months

• Serious infections

  Infections requiring hospitalization, intravenous antibiotic use, or prolonged antibiotic use for treatment of an infection for at least 30 days.

  36 months

Secondary Outcomes (7)

• Relapses

  36 months

• IgG and IgM levels

  36 months

• Infections

  36 months

• No Evidence of Disease Activity (NEDA-3)

  36 months

• Neurofilament light (NfL) and Glial Fibrillary Acid Protein (GFAP)

  36 months

Other Outcomes (6)

• Symbol Digital Modalities Test

  36 months

• 9-hole peg test

  36 months

• 25-foot walk speed

  36 months

Study Arms (2)

Ozanimod de-escalation of anti-CD20 treatment

EXPERIMENTAL

Ozanimod will be started 6-12 months after the last anti-CD20 infusion, including ocrelizumab subcutaneous injection, or 30-180 days from their last ofatumumab injection. Ozanimod will be provided by the study.

Drug: Ozanimod

Continued anti-CD20 treatment

NO INTERVENTION

Patients will continue to receive anti-CD20. Propensity score matched to the experimental arm.

Interventions

Ozanimod DRUG

De-escalation of anti-CD20 treatment using ozanimod.

Also known as: Zeposia

Ozanimod de-escalation of anti-CD20 treatment

Eligibility Criteria

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

You may qualify if:

• Participants have been diagnosed with relapsing forms of MS and have had multiple sclerosis related symptoms at least 3 years prior to baseline visit
• Male or female participants \> or = to 18 years of age at the time of initiation of de-escalation
• Participants do not have evidence of new inflammatory disease activity (no new T2/contrast enhancing lesions, absence of relapses) for a minimum of two years prior to de-escalation
• Participant is taking an anti-CD20 therapy as a DMT continuously for a minimum of two years (e.g., has received at least 3 courses of rituximab, ocrelizumab, ublituximab; 24 months of treatment with ofatumumab; or a combination of treatments whereby the patient has been deemed to be B-cell depleted for 2 years) prior to initiation of de-escalation
• Participants received their last anti-CD20 infusion, including ocrelizumab subcutaneous injection, within 6-12 months or received their last ofatumumab injection within 30 -180 days from Day 1
• Participants must provide written informed consent and be able to comply with the visit schedule and study related assessments
• Participants must be able to undergo a brain MRI without anesthesia
• Woman of Childbearing Potential must agree to practice a highly effective method of contraception throughout the study until completion and willing to follow pregnancy precautions.

You may not qualify if:

• Any progression of neurological disability in the year prior to the screening visit that would be consistent with progressive MS
• Participant has an EDSS \>6.5
• Participant has a history of other chronic neurological illnesses that might mimic MS with chronic or intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.)
• Participant is considering pregnancy in the short term, is pregnant, lactating or has a positive serum beta human chorionic gonadotropin (B-hCG) measured during screening.
• Participant has any other significant medical or psychiatric illness, if uncontrolled, that could jeopardize a subject's health or put them at significant safety risk during the course of the study in the opinion of treating investigator. Examples: uncontrolled hypertension, uncontrolled diabetes, uncontrolled asthma, uncontrolled depression
• Participant has a history of cancer within the last 5 years, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin or cervical dysplasia/cancer that has been excised and resolved)
• Participant has a history in the last 6 months of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure
• Participant has Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
• Participant has severe untreated sleep apnea
• Participant has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) \> 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy, or a history of uveitis
• Participant has a history or known presence of recurrent or chronic infection (e.g., hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV); recurrent urinary tract infections are allowed.
• Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a confirmed or suspected progressive multifocal leukoencephalopathy (PML). Known currently active tuberculosis (TB). History of incompletely treated Mycobacterium tuberculosis (TB) infection, as indicated by: Subject's medical records documenting incomplete treatment for Mycobacterium TB; Subject's self-reported history of incomplete treatment for Mycobacterium TB; Subjects with a history of TB who have undergone treatment accepted by the local health authorities (within 1 year from screening) may be eligible for study entry.
• Concomitant use of a monoamine oxidase inhibitor
• Use of systemic corticosteroids in the last 2 years, except for the use as a premedication for B-cell depleting treatment (Note: Use of inhaled or topical steroids; use of oral steroids for no greater than 14 days given for a non-MS condition are allowed)
• Prior use of alemtuzumab, mitoxantrone, cyclophosphamide, methotrexate, cyclosporine, or any experimental MS treatment within 5 half-lives

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (3)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Cleveland Clinic

Las Vegas, Nevada, 89106, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Interventions

ozanimod

Study Officials

• Enrique Alvarez, MD/PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Enrique Alvarez, MD/PhD

CONTACT

303-724-8249; enrique.alvarez@cuanschutz.edu

Lilli Farrell, BS

CONTACT

lillian.farrell@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Ozanimod de-escalation of anti-CD20 treatment vs continued treatment.

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: July 31, 2024
• Study Start: July 29, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
• Access Criteria: Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. For more information or to submit a request, please contact: clinicalresearchsupportcenter@ucdenver.edu

Locations

US (3)