Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Multiple Sclerosis Clinical Trial

Official title:

Evaluating the Immune Response to COVID19 Vaccination in Immunodeficient Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05286242
• Other study ID #: 2000029889
• Secondary ID: 2U19AI089992-112
• Status: Active, not recruiting
• Start date: February 10, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: February 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: June 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Multiple Sclerosis

Intervention

Biological:
• COVID19 vaccine
All participants receive one or more FDA-authorized COVID19 vaccinations according to standard of care and current medical recommendations. The intervention is not specifically administered as part of the study.

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (3)

Lead Sponsor	Collaborator
Yale University	National Institute of Allergy and Infectious Diseases (NIAID), Robert Leet and Clara Guthrie Patterson Trust

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in coronavirus disease 19 (COVID19) antibody titers over time	COVID 19 spike and neutralizing antibody titers will be monitored serially	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
Primary	Change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific T-cell activation over time	Flow cytometry characterizing immunophenotype of SARS-CoV2 specific T cells	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	Skin biopsy analysis	Histologic and immunologic characterization of skin biopsy specimens, comparing vaccinated to unvaccinated arm, at one or more timepoints post-vaccination	7 days post vaccine 1; 7 days post vaccine 2; 4 days post booster (all timepoints optional)
Secondary	Measurement of COVID19 antibodies in saliva	Descriptive assessment of whether COVID antibodies can be detected in saliva at any time point	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	Immune analysis	Deep immunologic assessment (flow cytometry, single cell RNA sequencing) of blood specimens; descriptive analysis at each timepoint with comparisons over time will be performed.	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	Changes in patient reported outcomes: COVID history	Subjective reports of vaccination-associated symptoms and COVID risk factors (COVID-19 survey)	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	Change in patient reported outcomes: patient reported disability steps	Subjects will complete Patient Derived Disability Step score	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	Change in patient reported outcomes: overall symptoms	SymptoMS screening questionnaire	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