Clinical trial NCT06529406: Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod
Official title: Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod (COAST: CD20 and Ozanimod Sequencing Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2024-07-31
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Ozanimod de-escalation of anti-CD20 treatment vs continued treatment.
Primary purpose: TREATMENT

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.

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.

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 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. (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)

Primary outcomes:
measure: New T2 lesions count
timeFrame: 36 months
measure: Serious infections
timeFrame: 36 months
Secondary outcomes:
measure: Relapses
timeFrame: 36 months
measure: IgG and IgM levels
timeFrame: 36 months
measure: Infections
timeFrame: 36 months
measure: No Evidence of Disease Activity (NEDA-3)
timeFrame: 36 months
measure: Neurofilament light (NfL) and Glial Fibrillary Acid Protein (GFAP)
timeFrame: 36 months
measure: Brain parenchymal and thalamic volume loss
timeFrame: 36 months
measure: Adverse Events
timeFrame: 36 months
Other outcomes:
measure: Symbol Digital Modalities Test
timeFrame: 36 months
measure: 9-hole peg test
timeFrame: 36 months
measure: 25-foot walk speed
timeFrame: 36 months
measure: Multiple Sclerosis Functional Composite (MSFC)
timeFrame: 36 months
measure: PRO outcomes
timeFrame: 36 months
measure: Changes in employment
timeFrame: 36 months.
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Las Vegas
country: United States
facility: Cleveland Clinic
state: Nevada
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: University of Colorado, Denver
name: Enrique Alvarez, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: