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Multiple SclerosisNCT04843774

Vaccine-generated Immunity in Ocrelizumab-treated Patients: Longitudinal Assessments (VIOLA)

An observational study of Multiple Sclerosis, run by NYU Langone Health at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a novel coronavirus and the causative agent of COVID 19 disease, whose presentation symptoms range from asymptomatic infection to mild flu-like symptoms to multi system failure and death, resulting in significant morbidity and mortality worldwide. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
SARS-COV-2 mRNA Vaccine
Type of treatment
Vaccines
How many people
64 participants
Where
2 sitesUnited States
Study dates
20 Apr 2021to 18 Apr 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: COVID-negative Multiple Sclerosis patients treated with ocrelizumab

Who may be able to join

  • Ability to provide written informed consent and understand and agree to be compliant with the study protocol
  • Age 18 to 65 years at time of signing the ICF
  • For women of childbearing potential: agreement to avoid in-vitro fertilization or 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
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
  • The following are acceptable contraceptive methods (as defined by the guidelines): progesterone-only hormonal contraception, where inhibition of ovulation is not the primary mode of action; male or female condom with or without spermicide; and cap, diaphragm, or sponge with spermicide. More effective contraceptive methods (e.g., bilateral tubal ligation; male sterilization; copper intrauterine devices) may be used, but are not required.
  • Diagnosis of RMS, PPMS, SPMS currently on ocrelizumab therapy
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  • Patients on ocrelizumab as SOC with the last dose received within 6 months prior to first vaccine
  • EDSS <= 6.5
  • Able to comply with study procedures based on the assessment of the Investigator
  • Healthy adults or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.

Who cannot join

  • MS related
  • Clinical MS relapse as defined by the treating physician, documented within the last 3 months prior to vaccine
  • Is acutely ill or febrile 72 hours prior to or at screening. Fever is defined as a body temperature >=38.0C/100.4F. Participants meeting this criterion may be rescheduled within the relevant window periods. Febrile participants with minor illnesses can be enrolled at the discretion of the investigator.
  • Is pregnant or breastfeeding; women of childbearing potential must have a negative serum or urine pregnancy test result within 14 days prior to study enrollment
  • Known history of SARS-CoV-2 infection as defined by:
  • Meeting CDC Clinical Case Definition Criteria (CDC, 2020) in which at least two core symptoms below are present:
Show all 44Show fewer
  • New continuous cough,
  • Temperature >= 37.8C,
  • Loss of, or change in, normal sense of smell (anosmia) or taste (ageusia) in the absence of alternative explanation,
  • Additional features such as influenza-like illness, clinical or radiological evidence of pneumonia, or acute worsening of underlying respiratory illness, or fever without another cause, AND
  • Objective evidence that supports COVID 19 diagnosis, such as detection of SARS-CoV-2 specific antibody in serum, plasma, or whole blood; radiographic evidence of pneumonia or acute respiratory distress syndrome.
  • Prior mRNA vaccine for COVID 19
  • History of a delayed second dose of vaccine >= 14 days from recommended dosing
  • Prior administration of an investigational coronavirus (SARS CoV, MERS CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID 19
  • Demonstrated inability to comply with the study procedures
  • Known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients
  • Bleeding disorder considered a contraindication to intramuscular injection or phlebotomy
  • Has received or plans to receive a non-study vaccine within 28 days prior to or after any dose of COVID vaccine (except for seasonal influenza vaccine, which is not permitted within 14 days before or after any dose of COVID vaccine)
  • Has participated in an interventional clinical study within 28 days prior to the day of enrollment
  • Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections (HIV-positive participants with CD4 count >=350 cells/mm^3 and an undetectable HIV viral load within the past year [low-level variations from 50 to 500 viral copies that do not lead to changes in antiretroviral therapy are permitted])
  • Has received systemic steroids or other immunosuppressants other than those required as ocrelizumab pre-medication for >14 days in total within 6 months prior to screening (for corticosteroids >=20 mg/day of prednisone equivalent)
  • Has received high-dose intravenous (IV) or oral steroids within 30 days of screening; IVIG or PLEX within 3 months of screening
  • Has received systemic immunoglobulins or blood products within 3 months prior to the day of screening
  • Patients cannot receive other COVID 19 vaccine products outside this study during the study period
  • Infection related
  • 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
  • Cancer Related
  • History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix or the uterus that have been excised and resolved with documented clean margins on pathology)
  • Other medical conditions
  • History of or currently active primary or secondary immunodeficiency
  • History of active alcohol or other drug abuse
  • Any concomitant, non-MS 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), and gastrointestinal
  • Known presence or history of other neurologic disorders, including but not limited to, the following:
  • Neuromyelitis optica spectrum disorders (NMOSD)
  • Severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression)
  • Psychosis not yet controlled by a treatment
  • Prior DMT for MS
  • Previous treatment with alemtuzemab, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
  • Treatment with another anti-CD 20 depleting agent within 6 months
  • Laboratory - Certain laboratory abnormalities or findings at screening, including the following:
  • IgG <300, or patients trending toward <300 based on previous labs/trajectory (PI discretion) at time of screening labs
  • Absolute lymphocyte count <750/mm3 at time of screening labs
  • Absolute neutrophil count <1000/mm3 at time of screening labs

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Colorado, Denver (UCD)

    Denver, Colorado, 80204

  • NYU Langone Health Multiple Sclerosis Comprehensive Care Center (NYULH MSCCC)

    New York, New York, 10016

Other trials in United States

About this study

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a novel coronavirus and the causative agent of COVID 19 disease, whose presentation symptoms range from asymptomatic infection to mild flu-like symptoms to multi system failure and death, resulting in significant morbidity and mortality worldwide. Novel vaccines against the SARS-CoV-2 virus have very recently been developed; however, the effectiveness, immune response, and short- or long-term safety of these vaccines have not been tested in immunocompromised patients on anti-CD-20 therapy for multiple sclerosis (MS) or for other disorders.

This study will examine the immune response of the Pfizer-BioNTech and Moderna messenger RNA (mRNA)-platform vaccines developed against SARS-CoV-2 virus given as standard of care (SOC) in MS patients on ocrelizumab.

Being tested
SARS-COV-2 mRNA Vaccine
Keywords
SARS-CoV-2 Vaccine, Ocrelizumab
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SARS-COV-2 mRNA VaccineDrug

    Pfizer-BioNTech and Moderna messenger RNA (mRNA)-platform vaccines developed against SARS-CoV-2 virus will be given as standard of care (SOC)

Study groups in NCT04843774
Study groupRoleWhat they receive
COVID-negative Multiple Sclerosis patients treated with ocrelizumabNot described
Receives: Drug: SARS-COV-2 mRNA Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Anti-SARS-CoV-2 S Titer Levels

    Measured: Baseline, Pre-First Vaccine Dose

  2. Anti-SARS-CoV-2 S Titer Levels

    Measured: Week 4, Post-Last Dose of Vaccine

  3. Anti-SARS-CoV-2 S Titer Levels

    Measured: Week 12, Post-Last Dose of Vaccine

  4. Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers

    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers

    Measured: Baseline, Pre-First Vaccine Dose

  5. Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers

    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers

    Measured: Week 4, Post-Last Dose of Vaccine

  6. Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers

    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers

    Measured: Week 12, Post-Last Dose of Vaccine

  7. T-Cell Response

    T-cell response will be measured by ELISpot assay

    Measured: Baseline, Pre-First Vaccine Dose

  8. T-Cell Response

    T-cell response will be measured by ELISpot assay

    Measured: Week 4, Post-Last Dose of Vaccine

  9. T-Cell Response

    T-cell response will be measured by ELISpot assay

    Measured: Week 12, Post-Last Dose of Vaccine

Secondary outcomes (2)

  1. SARS-CoV-2 anti-S1 and anti-Receptor Binding Domain (RBD) binding antibody levels

    Measured: Week 4, Post-Last Dose of Vaccine

  2. SARS-CoV-2 anti-S1 and anti-Receptor Binding Domain (RBD) binding antibody levels

    Measured: Week 12, Post-Last Dose of Vaccine

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2021
  2. Study start20 Apr 2021
  3. Primary completion18 Apr 2023
  4. Study completion18 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04843774
Sponsor's protocol ID
21-00206
Status last verified
Nov 2023
First submitted
9 Apr 2021
Last updated
8 Nov 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Curtin R, Velmurugu Y, Dibba F, Hao Y, Sreenivasaiah C, Khodadadi-Jamayran A, Nyovanie S, Kim A, Samanovic ML, Mulligan M, Priest J, Cabatingan M, Winger RC, Patskovsky Y, Kister I, Silverman GJ, Krogsgaard M. Persistent Classical and Atypical Memory B Cells Underlie Heterogeneous Vaccine Responses in Ocrelizumab-Treated Multiple Sclerosis. bioRxiv [Preprint]. 2025 Nov 4:2025.11.03.686372. doi: 10.1101/2025.11.03.686372.

    PubMed 41279857

Questions about this trial

What is this clinical trial studying?

An observational study of Multiple Sclerosis, run by NYU Langone Health at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Anti-SARS-CoV-2 S Titer Levels (time frame: Baseline, Pre-First Vaccine Dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04843774, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2023.

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