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

NCT04843774 | Completed FDA Drug

• 1 other identifier: 21-00206
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Multiple Sclerosis

Keywords

SARS-CoV-2 Vaccine; Ocrelizumab

Outcome Measures

Primary Outcomes (9)

• Anti-SARS-CoV-2 S Titer Levels

  Baseline, Pre-First Vaccine Dose

• Anti-SARS-CoV-2 S Titer Levels

  Week 4, Post-Last Dose of Vaccine

• Anti-SARS-CoV-2 S Titer Levels

  Week 12, Post-Last Dose of Vaccine

• 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

  Baseline, Pre-First Vaccine Dose

• 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

  Week 4, Post-Last Dose of Vaccine

• 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

  Week 12, Post-Last Dose of Vaccine

• T-Cell Response

  T-cell response will be measured by ELISpot assay

  Baseline, Pre-First Vaccine Dose

• T-Cell Response

  T-cell response will be measured by ELISpot assay

  Week 4, Post-Last Dose of Vaccine

• T-Cell Response

  T-cell response will be measured by ELISpot assay

  Week 12, Post-Last Dose of Vaccine

Secondary Outcomes (2)

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

  Week 4, Post-Last Dose of Vaccine

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

  Week 12, Post-Last Dose of Vaccine

Study Arms (1)

COVID-negative Multiple Sclerosis patients treated with ocrelizumab

Drug: SARS-COV-2 mRNA Vaccine

Interventions

SARS-COV-2 mRNA Vaccine DRUG

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

COVID-negative Multiple Sclerosis patients treated with ocrelizumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

COVID-negative Multiple Sclerosis patients treated with ocrelizumab

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (2)

University of Colorado, Denver (UCD)

Denver, Colorado, 80204, United States

Location

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

New York, New York, 10016, United States

Location

Related Publications (1)

• 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.

  PMID: 41279857 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Patients will have 5 blood draws in-person

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

CVnCoV COVID-19 vaccine

Condition Hierarchy (Ancestors)

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

Study Officials

• Ilya Kister, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 14, 2021
• Study Start: April 20, 2021
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: November 8, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)