Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Active, not recruiting

• Conditions: Multiple Sclerosis; Autoimmune Blistering Disease; B-Cell Deficiency
• Interventions: Biological: COVID19 vaccine

• Registration Number: NCT05286242
• Lead Sponsor: Yale University

Brief Summary

The purpose of this study is to understand the immune response to coronavirus disease-19 (COVID-19) vaccination in patients on B-cell depleting therapies (BCDT) over time, which in the future may help to inform clinical decision making in this patient population.

Detailed Description

This will be a prospective, observational cohort study consisting of individuals with autoimmune diseases who are undergoing treatment with anti-CD20 medications at the time they receive a vaccine against COVID-19. Control groups will include healthy individuals, individuals with autoimmune diseases on other immunomodulators, and individuals with autoimmune diseases not on immunotherapy.

Participants will undergo serial blood draws and saliva collections at prespecified time points surrounding vaccination. A subset of agreeable participants will undergo skin biopsy within days of the first vaccination, with the option to repeat skin biopsy after the second vaccination. Additional blood, saliva and skin biopsy specimens may be obtained after booster vaccinations or after known COVID19 infections .

Specimens collected will be used for studies aimed at (1) understanding the pathobiology of neurologic/inflammatory/immune diseases and the immunologic response to COVID-19 vaccination, (2) identifying how and why treatments used for neurologic/immune diseases may impact the effectiveness of vaccination, and (3) identifying dermatologic manifestations of the immunologic response to the COVID-19 mRNA vaccine.

The investigators are investigating both the production of antibodies against the virus over time and deeply interrogating the T-cell response to vaccination using methods that measure T-cell reactivity to the COVID-19 virus, including single cell RNA sequencing.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2021-02-10
• Study First Submitted: 2022-03-15
• Study First Submitted QC: 2022-03-16
• Study First Posted: 2022-03-18
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2026-05-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

Not provided

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Exclusion Criteria

• Use of high dose steroids for treatment of neurologic/immunologic disease within 1 month of COVID-19 vaccination
• Anti-CD20 B-cell depleting therapy infused within 2 weeks of first study visit
• Inability to comply with the requirements of the protocol, in the opinion of the primary investigator

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy control	COVID19 vaccine	Healthy controls Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design.
B-cell depleted	COVID19 vaccine	Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with B-cell depleting anti-CD20 monoclonal antibodies. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design.
Disease control	COVID19 vaccine	Disease controls (individuals with a qualifying autoimmune condition, but not treated with any immunomodulator). Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design.
Other immunomodulator	COVID19 vaccine	Individuals with autoimmune disease (multiple sclerosis or autoimmune blistering disease) who are treated with a non-CD20 monoclonal antibody immunomodulator to treat their disease. Participants will receive COVID19 vaccination according to standard of care (any FDA approved vaccine). They will donate serial biospecimens before and after vaccination according to the study design.

Primary Outcome Measures

Name	Time	Method
Change in coronavirus disease 19 (COVID19) antibody titers over time	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	COVID 19 spike and neutralizing antibody titers will be monitored serially
Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	Flow cytometry characterizing immunophenotype of SARS-CoV2 specific T cells

Secondary Outcome Measures

Name	Time	Method
Skin biopsy analysis	7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional)	Histologic and immunologic characterization of skin biopsy specimens, comparing vaccinated to unvaccinated arm, at one or more timepoints post-vaccination
Measurement of COVID19 antibodies in saliva	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	Descriptive assessment of whether COVID antibodies can be detected in saliva at any time point
Immune analysis	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	Deep immunologic assessment (flow cytometry, single cell RNA sequencing) of blood specimens; descriptive analysis at each timepoint with comparisons over time will be performed.
Changes in patient reported outcomes: COVID history	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	Subjective reports of vaccination-associated symptoms and COVID risk factors (COVID-19 survey)
Change in patient reported outcomes: patient reported disability steps	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	Subjects will complete Patient Derived Disability Step score
Change in patient reported outcomes: overall symptoms	Baseline, 2 weeks post vaccine 1, pre-vaccine 2, 1 week post vaccine 2, 6 months post vaccine 2; pre- and 2 week post any additional vaccines	SymptoMS screening questionnaire

Trial Locations

Locations (1)

Yale University; 🇺🇸 New Haven, Connecticut, United States