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

• ClinicalTrials.gov Identifier: NCT04877496
• Recruitment Status: Recruiting
• First Posted: May 7, 2021
• Last Update Posted: June 2, 2021
• Sponsor: University Hospital Inselspital, Berne
• Information provided by (Responsible Party): University Hospital Inselspital, Berne

Tracking Information

• First Submitted Date: May 6, 2021
• First Posted Date: May 7, 2021
• Last Update Posted Date: June 2, 2021
• Actual Study Start Date: April 26, 2021
• Estimated Primary Completion Date: August 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2021)

Humoral immune response to SARS-CoV2 spike protein [ Time Frame: At least 4 weeks after completion of COVID19 vaccination ]

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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 6, 2021)

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

• 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: Responses to COVID19 Vaccination in Patients With a Treatment History of Rituximab.
• Official Title: Registry Study for COVID19 Vaccination Efficacy in Patients With a Treatment History of Rituximab.
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: 1 Month

Biospecimen

Retention:   Samples Without DNA

Description:

PBMC

• Sampling Method: Non-Probability Sample
• Study Population: Participating Centers / Participating Departments: all at Bern University Hospital Insel)

Condition

• COVID19 Vaccination
• Rituximab
• Immunosuppression

Intervention

• Drug: History of exposure to anti-CD20 treatment since 01/01/2010
  Intravenous treatment history of anti-CD20 treatment since 01/01/2010
• Biological: Completion of COVID19 vaccine at least 4 weeks ago
  Completion of COVID19 vaccination course at least 4 weeks ago.

Study Groups/Cohorts

• Immunocompetent controls
  Participants aged at least 18 years, no history of COVID19, no history of anti-CD20 treatment
  Intervention: Biological: Completion of COVID19 vaccine 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
  Interventions:

  • Drug: History of exposure to anti-CD20 treatment since 01/01/2010
  • Biological: Completion of COVID19 vaccine at least 4 weeks ago

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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 6, 2021): 425
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2021
• Estimated Primary Completion Date: August 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Self-represented gender.

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Daniel Sidler, MD PhD; 0041316323144; daniel.sidler@insel.ch

Contact: Matthias B. Moor, MD PhD; 0041316323144; matthias.moor@insel.ch

• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT04877496
• Other Study ID Numbers: 4749
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital Inselspital, Berne
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital Inselspital, Berne
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Daniel Sidler, MD PhD; University Hospital Bern, Department of Nephrology and Hypertension

• PRS Account: University Hospital Inselspital, Berne
• Verification Date: May 2021