Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod (COAST)

Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod (COAST: CD20 and Ozanimod Sequencing Trial)

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Ozanimod

Detailed Description

Multicenter, Open Label, Prospective Study examining the safety and efficacy of de-escalation therapy to ozanimod (Zeposia®) over 36 months from anti-CD20 therapy for stable patients with relapsing forms of MS. A comparison to patients continuing anti-CD20 treatment was performed with propensity scoring to a cohort of at least 500 patients followed at Cleveland Clinic and the University of Colorado who also meet the above the inclusion and exclusion criteria. Patients were followed for 36 months.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Enrique Alvarez, MD/PhD; Phone Number: 303-724-8249; Email: enrique.alvarez@cuanschutz.edu
• Study Contact Backup: Name: Lilli Farrell, BS; Email: lillian.farrell@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Enrique Alvarez, MD/PhD; Phone Number: 303-724-8249; Email: enrique.alvarez@cuanschutz.edu
      • Contact: Haley Steinert; Phone Number: 303-724-4644; Email: neuroresearch@cuanschutz.edu
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Carrie M Hersh, DO
      • Contact: Liza Mercurio; Phone Number: 725-373-1590; Email: mercurl2@ccf.org
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Devon S Conway, MD; Phone Number: 216-636-1158; Email: conwayd2@ccf.org
      • Principal Investigator: Devon S Conway, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Exclusions related to Medications:

• 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
• Prior allergy to ozanimod

Exclusions related to Laboratory results:

• Participant has IgG levels <400 mg/dL
• Participant has neutrophils < 1500/μL (1.5 GI/L)
• Participant has an absolute white blood cell (WBC) count < 3500/μL (3.5 GI/L)
• Participant has an absolute lymphocyte count (ALC) < 800 cells/μL (0.80 GI/L).
• Participant has liver function impairment or persisting elevations of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) results > 3 x the upper limit of normal (ULN)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Continued anti-CD20 treatment; Patients will continue to receive anti-CD20. Propensity score matched to the experimental arm.
Experimental: Ozanimod de-escalation of anti-CD20 treatment; 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; De-escalation of anti-CD20 treatment using ozanimod.; Other Names: Zeposia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapses	Protocol and/or suspected relapses	36 months
IgG and IgM levels	IgG and IgM levels	36 months
Infections	All infections including opportunistic infections.	36 months
No Evidence of Disease Activity (NEDA-3)	Not meeting any of the following criteria: Evidence of Relapse activity - collected every 3 months via phone calls/clinic visits.; MRI disease activity - presence of new T2 lesions from MRI scans conducted at any timepoint.; 6 months Confirmed Disability progression (CDP6): measured by the EDSS assessed at baseline and every 6 months. CDP6 is defined as an increase in Expanded Disability Status Scale (EDSS) score of ≥1.5 if baseline EDSS was 0; or ≥1.0 points if baseline EDSS was ≥0.5-≤5.5; or by ≥0.5 points if baseline EDSS ≥6, sustained over two consecutive visits.	36 months
Brain parenchymal and thalamic volume loss	Brain parenchymal and thalamic volume loss	36 months
Adverse Events	Adverse Events	36 months
Neurofilament light (NfL) and Glial Fibrillary Acid Protein (GFAP)	Neurofilament light (NfL) and Glial Fibrillary Acid Protein (GFAP)	36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symbol Digital Modalities Test	A 4 points or 10% change in cognition	36 months
9-hole peg test	A 20% change in hand function	36 months
25-foot walk speed	A 20% change in walking speed	36 months
Multiple Sclerosis Functional Composite (MSFC)	A change in any of the above three criteria	36 months
PRO outcomes	Include treatment satisfaction (TSQM), MS fatigue scale (Modified Fatigue Impact Scale [MFIS]), or quality of life (MSIS-29). A minimum of 5% change.	36 months
Changes in employment	Changes in employment and full employment status.	36 months.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Enrique Alvarez, MD/PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sphingosine 1 Phosphate Receptor Modulators; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; ozanimod
• Other Study ID Numbers: 23-1686

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with interest in multiple sclerosis. Data or samples shared will be coded with no PHI included. Approval of the request and execution of all applicable agreements are prerequisites to the sharing of data with the requesting party.
• IPD Sharing 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.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes