Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod

Launched by UNIVERSITY OF COLORADO, DENVER · Jul 26, 2024

Keywords

ClinConnect Summary

This clinical trial is looking at the safety and effectiveness of a medication called ozanimod for patients with relapsing forms of multiple sclerosis (MS) who have been stable for some time after receiving anti-CD20 therapies, like rituximab or ocrelizumab. The goal is to see if switching to ozanimod can help these patients while reducing the intensity of their treatment. The trial is currently recruiting participants who are at least 18 years old, have been diagnosed with relapsing MS for at least three years, and have not had any new MS-related issues for the past two years.

To participate, individuals need to have been on anti-CD20 treatment for at least two years and have completed their last infusion within the past year. They should also be able to undergo an MRI scan without sedation. Participants will be closely monitored throughout the study to assess their health and the effects of ozanimod. Women who could become pregnant must agree to use effective contraception during the trial. This study is important because it may provide new insights into managing MS in patients who have been stable after previous treatments.

Gender

ALL

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)