Clinical trial NCT05286242: Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients
Official title: Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Multiple Sclerosis
Autoimmune Blistering Disease
B-Cell Deficiency
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Robert Leet and Clara Guthrie Patterson Trust
First posted: 2022-03-18
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: There will be four groups of participants overall:

* Patients with autoimmune neurologic/autoimmune blistering disease (AIBD) who are on B-cell depleting therapy (anti-CD20 monoclonal antibodies)
* Patients with autoimmune neurologic/AIBD who are on other types of immunomodulators
* Patients with autoimmune neurologic/AIBD who are untreated
* Healthy controls

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.

Eligibility criteria: Subjects with neurologic/immunologic condition:

* at least 18 years of age
* Known diagnosis of autoimmune neurologic disease (e.g. multiple sclerosis (MS), neuromyelitis optica, myelin oligodendrocyte glycoprotein (MOG) -associated disorder) or autoimmune blistering disease (AIBD).
* EITHER:

  * Treated with an anti-CD20 (rituximab, ocrelizumab) medications for \>6 months at the time of vaccination (B-cell depletion therapy, BCDT)
  * On no immunomodulatory therapy for their autoimmune condition for \>6 months at the time of vaccination
  * Treated with a non-BCDT immunotherapy
* No relapse of neurologic/immunologic disease for \>6 months prior to the time of enrollment
* Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team.
* No active skin condition (e.g. open sores) preventing blood draw

Healthy Controls:

* at least 18 years of age
* No evidence of neurological/immunologic disease/illness/condition
* Subject is eligible and willing to receive COVID-19 vaccination in accordance with local and national guidelines, or subject intends to receive booster COVID-19 vaccination in accordance with recommendations from their primary medical team.
* No active skin condition (e.g. open sores) preventing blood draw/skin biopsy

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

Primary outcomes:
measure: Change in coronavirus disease 19 (COVID19) antibody titers over time
timeFrame: 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
measure: Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time
timeFrame: 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
Secondary outcomes:
measure: Skin biopsy analysis
timeFrame: 7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional)
measure: Measurement of COVID19 antibodies in saliva
timeFrame: 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
measure: Immune analysis
timeFrame: 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
measure: Changes in patient reported outcomes: COVID history
timeFrame: 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
measure: Change in patient reported outcomes: patient reported disability steps
timeFrame: 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
measure: Change in patient reported outcomes: overall symptoms
timeFrame: 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
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Erin Longbrake
role: PRINCIPAL_INVESTIGATOR
References: