RECRUITING

Effects of Ocrelizumab Treatment on Immune Cells in Lymph Nodes in Multiple Sclerosis

Conditions

Multiple Sclerosis, Relapsing-Remitting Ocrelizumab Lymph node Lymphocyte

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

B cell-depleting therapies, such as ocrelizumab, are among the most effective medications currently available for the treatment of multiple sclerosis (MS). This suggests that B cells play a very important role in MS. While B cells are rapidly eliminated from the blood of patients treated with medications like ocrelizumab, little is known about how effectively B cells are eliminated from lymph nodes, which are important sites of B cell activation. This study is being conducted to determine to what extent B cells are targeted in lymph nodes following ocrelizumab treatment, which may have important consequences for long-term MS outcomes.

Official Title

Identifying Ocrelizumab-resistant Lymphocytes in Lymphoid Tissue in Multiple Sclerosis

Quick Facts

Study Start:2025-02-04

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06495593

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Ability to provide written informed consent and be compliant with the study protocol * The treating neurologist's independent medical assessment and decision to initiate the patient on ocrelizumab treatment as most appropriate standard of care for the patient * Diagnosis of RR-MS with Expanded Disability Status Scale (EDSS) 0-5.5 at enrollment * Treatment-naïve (i.e. no prior disease modifying therapy) * Disease duration from the onset of MS symptoms: less than 15 years in patients with an EDSS greater than 5.0 at screening * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab	* Diagnosis of secondary progressive MS without relapses for at least 1 year. * Diagnosis of primary progressive MS. * Prior treatment with any disease modifying therapy for MS. * Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency). * Known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis). * History of recurrent aspiration pneumonia requiring antibiotic therapy. * History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy). * Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit. * Pregnant or lactating, or intending to become pregnant during the study * Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study drug. * On systemic anti-coagulation or known blood clotting disorder. * History of or currently active primary or secondary immunodeficiency. * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. * History of alcohol or other drug abuse within 24 weeks prior to enrollment. * History or known presence of systemic autoimmune disorders, potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren's syndrome, Behçet's disease). * Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. * Significant, uncontrolled disease, as defined by AMA guidelines or similar, such as cardiovascular (including congestive heart failure - NYHA grade 3 or 4, cardiac arrhythmia), uncontrolled hypertension, pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), gastrointestinal, or any other significant disease. * Known presence or history of other neurologic disorders * Systemic corticosteroid therapy within 4 weeks prior to baseline. * Contraindications for, or intolerance to, oral or IV corticosteroids, including IV methylprednisolone, according to the country label, including hypersensitivity to any of the treatment drug constituents. * Previous treatment with cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation. * Positive serum or urine β-hCG. * Positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] positive or hepatitis B core antibody \[total HBcAb\] confirmed by positive viral DNA polymerase chain reaction \[PCR\]). * AST or ALT more than 2 times the upper limit of normal. * Platelet count below lower limit of normal. * Total white blood cell count, including differential counts, below lower limit of normal. * Absolute neutrophil count below lower limit of normal. * Lymphocyte count below lower level of normal. * Levels of serum IgG 18% below the lower limit of normal (LLN) and levels of serum IgM 8% below the LLN. * Absolute CD4+ and CD8+ counts and CD4:CD8 ratio - within normal limits.

Inclusion Criteria

Exclusion Criteria

* Ability to provide written informed consent and be compliant with the study protocol
* The treating neurologist's independent medical assessment and decision to initiate the patient on ocrelizumab treatment as most appropriate standard of care for the patient
* Diagnosis of RR-MS with Expanded Disability Status Scale (EDSS) 0-5.5 at enrollment
* Treatment-naïve (i.e. no prior disease modifying therapy)
* Disease duration from the onset of MS symptoms: less than 15 years in patients with an EDSS greater than 5.0 at screening
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab

* Diagnosis of secondary progressive MS without relapses for at least 1 year.
* Diagnosis of primary progressive MS.
* Prior treatment with any disease modifying therapy for MS.
* Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency).
* Known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis).
* History of recurrent aspiration pneumonia requiring antibiotic therapy.
* History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, HTLV-1, herpes zoster myelopathy).
* Known active bacterial, viral, fungal, mycobacterial infection, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit.
* Pregnant or lactating, or intending to become pregnant during the study
* Women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to initiation of study drug.
* On systemic anti-coagulation or known blood clotting disorder.
* History of or currently active primary or secondary immunodeficiency.
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
* History of alcohol or other drug abuse within 24 weeks prior to enrollment.
* History or known presence of systemic autoimmune disorders, potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren's syndrome, Behçet's disease).
* Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
* Significant, uncontrolled disease, as defined by AMA guidelines or similar, such as cardiovascular (including congestive heart failure - NYHA grade 3 or 4, cardiac arrhythmia), uncontrolled hypertension, pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), gastrointestinal, or any other significant disease.
* Known presence or history of other neurologic disorders
* Systemic corticosteroid therapy within 4 weeks prior to baseline.
* Contraindications for, or intolerance to, oral or IV corticosteroids, including IV methylprednisolone, according to the country label, including hypersensitivity to any of the treatment drug constituents.
* Previous treatment with cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation.
* Positive serum or urine β-hCG.
* Positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] positive or hepatitis B core antibody \[total HBcAb\] confirmed by positive viral DNA polymerase chain reaction \[PCR\]).
* AST or ALT more than 2 times the upper limit of normal.
* Platelet count below lower limit of normal.
* Total white blood cell count, including differential counts, below lower limit of normal.
* Absolute neutrophil count below lower limit of normal.
* Lymphocyte count below lower level of normal.
* Levels of serum IgG 18% below the lower limit of normal (LLN) and levels of serum IgM 8% below the LLN.
* Absolute CD4+ and CD8+ counts and CD4:CD8 ratio - within normal limits.

Contacts and Locations

Study Contact

Joseph Sabatino, MD, PhD

CONTACT

(415) 353-2069

joseph.sabatinojr@ucsf.edu

Principal Investigator

Joseph Sabatino, MD, PhD

PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Study Locations (Sites)

University of California, San Francisco

San Francisco, California, 94158

United States

Collaborators and Investigators

Sponsor: University of California, San Francisco

Joseph Sabatino, MD, PhD, PRINCIPAL_INVESTIGATOR, University of California, San Francisco

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-04

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2025-02-04

Study Completion Date2025-12-31

Terms related to this study

Keywords Provided by Researchers

Ocrelizumab
Lymph node
Lymphocyte

Additional Relevant MeSH Terms

Multiple Sclerosis, Relapsing-Remitting