Evaluating ozanimod for stable MS patients previously treated with anti-CD20 therapies

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

This study is testing if switching to a new medication called ozanimod can be a safe and effective option for stable multiple sclerosis patients who have been using anti-CD20 therapies.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Colorado, Denver (Academic / other)
• Drugs / interventions: rituximab, ocrelizumab, ublituximab, ofatumumab, alemtuzumab, methotrexate, cyclophosphamide
• Locations: 3 sites (Aurora, Colorado and 2 other locations)
• Trial ID: NCT06529406 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label, prospective study aims to assess the safety and efficacy of ozanimod as a de-escalation therapy for clinically stable patients with relapsing forms of multiple sclerosis who have been treated with anti-CD20 therapies. Over a period of 36 months, the study will compare outcomes of patients transitioning to ozanimod against those who continue their anti-CD20 treatment, utilizing a cohort of at least 500 patients from the Cleveland Clinic and the University of Colorado. Participants must have been stable without new disease activity for at least two years prior to the study.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with relapsing forms of MS who have been stable without new inflammatory activity for at least two years and have been on anti-CD20 therapy for a minimum of two years.

Not a fit: Patients who have experienced new inflammatory disease activity or have not been on anti-CD20 therapy for the required duration may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer and effective treatment option for patients with relapsing multiple sclerosis by allowing them to transition from anti-CD20 therapies to ozanimod.

How similar studies have performed: While the approach of de-escalating therapy in MS is being explored, this specific evaluation of ozanimod following anti-CD20 therapies is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

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)

Where this trial is running

Aurora, Colorado and 2 other locations

• University of Colorado Anschutz Medical Campus — Aurora, Colorado, United States (Recruiting)
• Cleveland Clinic — Las Vegas, Nevada, United States (Recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Enrique Alvarez, MD/PhD — University of Colorado, Denver
• Study coordinator: Enrique Alvarez, MD/PhD

Conditions Relapsing Multiple Sclerosis