Convalescent Antibody-Mediated Treatment of COVID-19 Infections in Patients with B-cell dysfunction, a Randomized Trial (COVID-Compromise Study).

Phase 2

Suspended

• Conditions: b-cell dysfunction; 10047954; 10021460; 10047438

• Registration Number: NL-OMON51203
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Suspended
• Sex: Not specified
• Target Recruitment: 86

Inclusion Criteria

- Patient is >= 18 years of age, diagnosed with COVID-19 based on a positive PCR
or antigen test in combination with COVID-19 related symptoms (e.g. Fever,
hypoxia, gastrointestinal symptoms).
- Hospitalized.
AND one of immunocompromised conditions/treatments below

B-cell inhibition related ICP
- Use of anti-CD19 or -CD20 directed antibody therapy in 6 months prior to
inclusion.
- Previous or current treatment with drugs that significantly impair B cell
function (e.g. ibrutinib, venetoclax, acalabrutinib, idelalisib etc) within 6
months prior to inclusion

Other immunosuppression/treatment related ICP
- Patients treated with bendamustine, purine analogues or anti-thymocyte
globulin within 6 months prior to inclusion.
- Solid organ transplant patients that are taking systemic immunosuppressive
drugs from at least three pharmacological classes. Or from at least two classes
in combination with negative anti-SARS-CoV-2 antibodies <= 96 hours prior to
inclusion.

Cellular therapy related ICP
- Allogeneic hematopoietic stem cell transplant (HSCT) in 12 months prior to
inclusion.
- HSCT for which systemic therapy against graft-versus-host-disease is used.
- Recipient of CAR-T cells < 2 years prior to inclusion.

Disease related ICP
- Chronic B-cell leukemia*s: CLL, HCL, PLL, multiple myeloma, Waldenströms
macroglobulinemia

Congenital ICP
- Congenital disorder resulting in severe B-cell dysfunction or depletion
requiring immunoglobulin suppletion (e.g. agammaglobulinemia).

Exclusion Criteria

- Patient or legal representative is unable to provide written informed consent
- Life expectancy of < 28 days in the opinion of the treating physician
- Has previously participated in this study.
- Has previously received convalescent plasma with high level neutralizing
anti-SARS-CoV-2 antibodies (either in other study or in compassionate use
program).
- Known IgA deficiency (defined as absence of IgA and possibility of anti-IgA
antibodies), patients with disease related reduced levels of IgA (e.g. in
myeloma or lymphoma) may be included in the study.
- Known previous grade 3 or 4 hypersensitivity reactions to treatment with
immunoglobulins
- Patient who has reached endpoint already at admission (direct adjunctive
oxygen therapy in the form of high-flow nasal oxygen (HFNO), mechanical
ventilation or ICU admission for other reason).

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The endpoint of this study is a severe course of disease, which is defined<br /><br>until day 28 after randomization:<br /><br>* Start of adjunctive ventilator support (HFNO, mechanical ventilation) or an<br /><br>indication to do so but due to due to previously agreed treatment restrictions<br /><br>HFNO or mechanical ventilation is not initiated..<br /><br>* Admission to an intensive care unit for progression of respiratory<br /><br>insufficiency..<br /><br>* No clinical improvement on day 7 after randomization or any day thereafter<br /><br>after first day of treatment (based on oxygen use in patients that require<br /><br>oxygen and based on clinical disease burden (including fever) in patients that<br /><br>require no oxygen).<br /><br>* Readmission for COVID-19. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Severity of COVID-19 disease in patients that have no anti SARS-CoV-2<br /><br>antibodies upon inclusion (*per protocol* analysis).<br /><br>* Duration of hospitalization.<br /><br>* 28 days overall mortality.<br /><br>* The four individual endpoints that compose the primary endpoint.<br /><br>* Time to complete recovery from COVID-19 related symptoms.<br /><br>* Rate of viral decay<br /><br>* Development of long-term persistent neutralizing antibodies against SARS-COV-2<br /><br>* T-cell immunity as measured by in vitro specific T cell response to COVID-19<br /><br>tetrameric antigens.</p><br>