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

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ClinicalTrials.gov Identifier: NCT04843774
Recruitment Status : Recruiting
First Posted : April 14, 2021
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date April 9, 2021
First Posted Date April 14, 2021
Last Update Posted Date May 12, 2021
Actual Study Start Date April 20, 2021
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 12, 2021)
  • Anti-SARS-CoV-2 S Titer Levels [ Time Frame: Baseline, Pre-First Vaccine Dose ]
  • Anti-SARS-CoV-2 S Titer Levels [ Time Frame: Week 4, Post-Last Dose of Vaccine ]
  • Anti-SARS-CoV-2 S Titer Levels [ Time Frame: Week 12, Post-Last Dose of Vaccine ]
  • Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers [ Time Frame: Baseline, Pre-First Vaccine Dose ]
    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers
  • Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers [ Time Frame: Week 4, Post-Last Dose of Vaccine ]
    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers
  • Number of participants with a fold rise of serum anti-SARS-CoV-2 S titers [ Time Frame: Week 12, Post-Last Dose of Vaccine ]
    This outcome measure will be reported for participants with a fold rise >=2, >=3, and >=4 of serum anti-SARS-CoV-2 S titers
  • T-Cell Response [ Time Frame: Baseline, Pre-First Vaccine Dose ]
    T-cell response will be measured by ELISpot assay
  • T-Cell Response [ Time Frame: Week 4, Post-Last Dose of Vaccine ]
    T-cell response will be measured by ELISpot assay
  • T-Cell Response [ Time Frame: Week 12, Post-Last Dose of Vaccine ]
    T-cell response will be measured by ELISpot assay
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 12, 2021)
  • SARS-CoV-2 anti-S1 and anti-Receptor Binding Domain (RBD) binding antibody levels [ Time Frame: Week 4, Post-Last Dose of Vaccine ]
  • SARS-CoV-2 anti-S1 and anti-Receptor Binding Domain (RBD) binding antibody levels [ Time Frame: Week 12, Post-Last Dose of Vaccine ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Vaccine-generated Immunity in Ocrelizumab-treated Patients: Longitudinal Assessments (VIOLA)
Official Title Vaccine-generated Immunity in Ocrelizumab-treated Patients: Longitudinal Assessments (VIOLA)
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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Patients will have 5 blood draws in-person
Sampling Method Non-Probability Sample
Study Population COVID-negative Multiple Sclerosis patients treated with ocrelizumab
Condition Multiple Sclerosis
Intervention Drug: SARS-COV-2 mRNA Vaccine
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/Cohorts COVID-negative Multiple Sclerosis patients treated with ocrelizumab
Intervention: Drug: SARS-COV-2 mRNA Vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 12, 2021)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date October 14, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. 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
    2. 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Zoe Rimler 929-455-5084 zoe.rimler@nyulangone.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04843774
Other Study ID Numbers 21-00206
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party NYU Langone Health
Study Sponsor NYU Langone Health
Collaborators Not Provided
Investigators
Principal Investigator: Ilya Kister, MD NYU Langone Health
PRS Account NYU Langone Health
Verification Date May 2021