Reduced Oligodendrocyte-specific Cytotoxicity and Ofatumumab Treatment

NCT05171972 | Completed

• 1 other identifier: HS-21-00540
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In this study the investigators wish to test the hypothesis that the repertoire of solutes secreted by leukocytes isolated from patients with relapsing-remitting forms of Multiple Sclerosis (MS) following 6 months of treatment with Ofatumumab (Kesimpta®) will be less toxic to mouse-derived oligodendrocyte lineage cells, grown in a dish, than solutes secreted by the same leukocyte populations prior to treatment with Ofatumumab.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Kesimpta; Ofatumumab

Outcome Measures

Primary Outcomes (1)

• Assessment of oligodendrocyte death and mitochondrial dysfunction comparing supernatant samples from patients after 6 months treatment (M06) to pre-treatment, drug naïve supernatants (M00) and to supernatants collected from healthy control subjects

  To determine if solutes secreted by T cells, monocytes, neutrophils or NK cells isolated from patients with relapsing-remitting forms of MS following 6 months (M06) of treatment with Ofatumumab are less toxic to mouse-derived oligodendrocytes and their progeny (OPC) than solutes secreted by the same sub-populations of leukocytes collected prior to treatment (M00 drug naive), and how this compares to samples from healthy control subjects.

  27 months

Secondary Outcomes (1)

• Identify factor(s) associated with oligodendrocyte and OPC stress/death

  27 months

Study Arms (2)

Relapsing-remitting Multiple Sclerosis

Enrolled subjects in this group will have clinically definite Multiple Sclerosis as defined by the revised McDonald criteria of the relapsing-remitting form with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 and will be treated with Ofatumumab.

Drug: Ofatumumab

Healthy Control Subjects

Enrolled subjects must not have clinically definite Multiple Sclerosis as defined by the revised McDonald criteria, any other autoimmune disease, demyelinating co-morbidity, neurological disease or immune system altering disease.

Interventions

Ofatumumab DRUG

This investigator-initiated study will be carried out secondary to the discussion of treatment with Ofatumumab and thus our study will not influence or impact the determination of the suitability for candidates to commence therapy with Ofatumumab. This decision will be made by the patient's physician as part of the patient's standard care, and will occur independently of this study. Patients to be enrolled in this longitudinal study will only be asked if they would like to take part if their clinician independently chooses Ofatumumab as a treatment option.

Also known as: Kesimpta

Relapsing-remitting Multiple Sclerosis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

For this prospective longitudinal study the investigators will recruit 20 patients with clinically definite relapsing-remitting MS (as defined by the revised McDonald criteria) who will be treated with Ofatumumab (Kesimpta). Patients will be recruited from the Multiple Sclerosis Comprehensive Care Center at USC Keck School of Medicine and the LAC+USC Medical Center, Multiple Sclerosis Clinic. The investigators will also recruit 20 healthy control (HC) subjects. Healthy controls will be age and sex matched to the RR-MS population as much as possible.

You may qualify if:

• RR-MS patients only:
• This investigator-initiated study/trial (IIT) will be carried out secondary to the discussion of treatment with Ofatumumab and thus our study will not influence or impact the determination of the suitability for candidates to commence therapy with Ofatumumab. This decision will be made by the patient's physician as part of the patient's standard care, and will occur independently of this study. Patients to be enrolled in this longitudinal study will only be asked if they would like to take part in this IIT if their clinician independently chooses Ofatumumab as a treatment option:
• Patients must have clinically definite Multiple Sclerosis as defined by the revised McDonald criteria of the relapsing-remitting form with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5.
• Patients must be treatment naive to Ofatumumab (Kesimpta)
• Patients must have the ability to understand and sign this study-specific IRB-approved informed consent form.
• Patients must be willing to donate \~80ml of blood each for M00 and M06 that will be used for testing the specific aims described in this proposal.
• Patients must have a lymphocyte count within the normal range at baseline (3.8-10.8 x1,000/ml)
• Healthy Control Subjects only:
• Patients must not have clinically definite Multiple Sclerosis as defined by the revised McDonald criteria, any other autoimmune disease, demyelinating co-morbidity, neurological disease or immune system altering disease (e.g. HIV).
• Patients must have the ability to understand and sign this study-specific IRB-approved informed consent form.
• Patients must be willing to donate \~80ml of blood at one time only that will be used for testing the specific aims described in this proposal.
• Patients must have a lymphocyte count within the normal range at baseline (3.8-10.8 x1,000/ml).

You may not qualify if:

• RR-MS patients only:
• Treatment with any of the following within 90 days of commencing treatment with Ofatumumab: teriflunomide (Aubagio®), IV immunoglobulin or plasmapheresis.
• Previous treatment with natalizumab (Tysabri®) within 30 days of commencing treatment with Ofatumumab.
• Documented relapse within 30 days prior to baseline.
• Systemic corticosteroid therapy within 4 weeks prior to baseline.
• Prior treatment with Mitoxantrone, Cyclophosphamide, Cyclosporine, Azathioprine or Methotrexate or any other immunosuppressant, or total body irradiation or bone marrow transplantation.
• Prior treatment with a B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab).
• Prior treatment with alemtuzumab (Lemtrada®).
• Current supplemental treatment with high dose biotin.
• Women who are pregnant, lactating, breast feeding or of childbearing age who do not consent to approved contraceptive use during the study.
• Prior or current treatment with a drug that is experimental
• Healthy Control Subjects:
• Treatment with any FDA-approved drug or experimental drug for any condition.
• Systemic corticosteroid therapy within 4 weeks prior to blood collection.
• Women who are pregnant, lactating, or could be pregnant.

Sponsors & Collaborators

• University of Southern California: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Southern California

Los Angeles, California, 90089, United States

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and Serum samples

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Eve Kelland, Ph.D.

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Research

Study Record Dates

• First Submitted: December 10, 2021
• First Posted: December 29, 2021
• Study Start: January 29, 2022
• Primary Completion: June 30, 2025
• Study Completion: July 31, 2025
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)