Responses to COVID19 Vaccination in Patients With a Treatment History of Rituximab. (RituxiVac)

Registry Study for COVID19 Vaccination Efficacy in Patients With a Treatment History of Rituximab.

Patients with treatment history of rituximab since 01.01.2019 and immunocompetent volunteers will be contacted to give a blood sample after their COVID19 vaccination, and in a subset also before vaccination. Immune responses of antibodies and SARS-CoV2-specific T-cells to the vaccination will be quantified and the rituximab effect on COVID19 vaccine-induced immune responses is analyzed.

Study Overview

• Status: Recruiting
• Conditions: Immunosuppression; Rituximab; COVID19 Vaccination
• Intervention / Treatment: Biological: Completion of COVID19 vaccine at least 4 weeks ago; Drug: History of exposure to anti-CD20 treatment since 01/01/2010

• Study Type: Observational
• Enrollment (Anticipated): 425

Contacts and Locations

• Study Contact: Name: Daniel Sidler, MD PhD; Phone Number: 0041316323144; Email: daniel.sidler@insel.ch
• Study Contact Backup: Name: Matthias B. Moor, MD PhD; Phone Number: 0041316323144; Email: matthias.moor@insel.ch

Study Locations

• Switzerland
  • BE
    • Bern, BE, Switzerland, 3010
      • Recruiting
      • University Hospital Bern Inselspital
      • Contact: Daniel Sidler, MD PhD; Phone Number: 00316323144; Email: daniel.sidler@insel.ch
      • Contact: Matthias B. Moor, MD PhD; Phone Number: 0316323144; Email: matthias.moor@insel.ch
      • Principal Investigator: Daniel Sidler, MD PhD
      • Sub-Investigator: Matthias B Moor, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participating Centers / Participating Departments: all at Bern University Hospital Insel)

Description

Inclusion Criteria:

1. Patients who were treated with anti-CD20 treatment since 01.01.2010
2. Patients who received a COVID19 vaccination (completion of all required doses) until target date (initial target: 30.05.21, but can be delayed to 30.06.21, 30.07.21 or 30.08.21 in case of insufficient enrollment)
3. Volunteers without a history of anti-CD20 treatment exposure
4. All: written informed consent.

Exclusion Criteria:

Exclusion criteria for patients (any of the following)

1. Patients aged 18 years and younger at time of study enrollment and/or
2. Pregnant or lactating women at time of study enrollment and/or
3. Patients who do not provide written informed consent and/or
4. Patients who have previously had a COVID19 infection (self-reported COVID19 disease, positive PCR or serology)
5. Patients who are in a dependency relationship with the study personnel (hierarchical, social)

Exclusion criteria for volunteers (any of the following)

1. Volunteers aged 18 years and younger at time of study enrollment and/or
2. Pregnant or lactating women at time of study enrollment and/or
3. Volunteers who do not provide informed consent and/or
4. Volunteers who suffer from an active autoimmune disease, active cancer, immunosuppressive therapy, history of anti-CD20 treatment and/or
5. Volunteers who have previously had a COVID19 infection (self-reported COVID19 disease, positive PCR or serology)
6. Volunteers who did not complete their COVID19 vaccination
7. Volunteers who are in a dependency relationship with the study personnel (hierarchical, social)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Immunocompetent controls; Participants aged at least 18 years, no history of COVID19, no history of anti-CD20 treatment	Biological: Completion of COVID19 vaccine at least 4 weeks ago; Completion of COVID19 vaccination course at least 4 weeks ago.
Patients with a treatment history of rituximab; Participants aged at least 18 years, no history of COVID19, history of at least 1 dose of anti-CD20 treatment received since 01/01/2010	Biological: Completion of COVID19 vaccine at least 4 weeks ago; Completion of COVID19 vaccination course at least 4 weeks ago.; Drug: History of exposure to anti-CD20 treatment since 01/01/2010; Intravenous treatment history of anti-CD20 treatment since 01/01/2010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral immune response to SARS-CoV2 spike protein	Percentage of all patients developing IgG antibodies against SARS-CoV2 spike protein that is comparable to the immunological response in immunocompetent controls (-2 standard deviations of mean)	At least 4 weeks after completion of COVID19 vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of IgG antibodies against SARS-CoV2 with age, history, co-medication and biomarkers of immunocompetence	Multivariable regression models for IgG antibodies against SARS-CoV2 with age, history, co-medication and biomarkers of immunocompetence as confounding variables.	At least 4 weeks after completion of COVID19 vaccination
Correlation of IgG antibodies against SARS-CoV2 with time interval since last dose of rituximab		At least 4 weeks after completion of COVID19 vaccination
Correlation of IgG antibodies against SARS-CoV2 with cumulative dose of rituximab received.		At least 4 weeks after completion of COVID19 vaccination
T cell anti-SARS-CoV2 response after COVID19 vaccination		At least 4 weeks after completion of COVID19 vaccination
Correlation between IgG antibodies against SARS-CoV2 and B-cell counts, T-cell counts and total immunoglobulin levels	Multivariable regression models for IgG antibodies against SARS-CoV2 with B-cell counts, T-cell counts and total immunoglobulin levels as confounders.	At least 4 weeks after completion of COVID19 vaccination

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Investigators: Principal Investigator: Daniel Sidler, MD PhD, University Hospital Bern, Department of Nephrology and Hypertension

Publications and helpful links

General Publications

• Sidler D, Born A, Schietzel S, Horn MP, Aeberli D, Amsler J, Moller B, Njue LM, Medri C, Angelillo-Scherrer A, Borradori L, Seyed Jafari SM, Radonjic-Hoesli S, Chan A, Hoepner R, Bacher U, Mani LY, Iype JM, Suter-Riniker F, Staehelin C, Nagler M, Hirzel C, Maurer B, Moor MB. Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy. RMD Open. 2022 Mar;8(1):e002166. doi: 10.1136/rmdopen-2021-002166.
• Moor MB, Suter-Riniker F, Horn MP, Aeberli D, Amsler J, Moller B, Njue LM, Medri C, Angelillo-Scherrer A, Borradori L, Radonjic-Hoesli S, Seyed Jafari SM, Chan A, Hoepner R, Bacher VU, Mani LY, Iype JM, Hirzel C, Maurer B, Sidler D. Humoral and cellular responses to mRNA vaccines against SARS-CoV-2 in patients with a history of CD20 B-cell-depleting therapy (RituxiVac): an investigator-initiated, single-centre, open-label study. Lancet Rheumatol. 2021 Nov;3(11):e789-e797. doi: 10.1016/S2665-9913(21)00251-4. Epub 2021 Sep 7. Erratum In: Lancet Rheumatol. 2022 Mar;4(3):e174.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2021
• Primary Completion (Anticipated): August 30, 2021
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 7, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Rituximab; T-cells; SARS-CoV2; B-cells; COVID19 vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 4749

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No