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

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A more severe course of COVID-19 infections has been reported in immunocompromised patients (ICPs), such as those suffering from innate immune disorders, (haematological) malignancies, or patients who are treated with immunosuppressive medication. The common denominator among these patients is an impaired B-cell or T-cell function, or depletion, and these patients are unable to generate sufficient neutralizing antiviral antibody titres or their production is delayed. To date, no specific therapeutic strategies have convincingly been shown effective in this patient population. Treatment with neutralizing antiviral antibodies from convalescent patients has been tested in the general population. In this population, one study has shown promising results when it is administered in the very first stages of disease, but not in hospitalized patients. This discrepancy is thought to result from the redundant effect of exogenous antibodies in these patients, in whom high titres of neutralizing antibodies are typically present at hospital admission. In those who are still antibody negative at admission, all but few start producing antibodies within days after admission as well. Since immunocompromised patients may not develop neutralizing antibodies, exogenously provided antibodies could be a functional adjuvant therapy of COVID-19, also in later stages of disease (e.g. upon hospitalization), but no trials to data have addressed this question. Study bjectives: To generate proof that convalescent antibody-mediated treatment of ICPs, who suffer from COVID-19 disease can protect from a severe course of disease. Study design: The trial is designed as a cohort specific, randomized, controlled, comparative, phase 2/3 study. Study population: This study includes ICPs of 18 years or older that are hospitalized for COVID-19. ICP is here defined as patients in whom the underlying disease itself or immunosuppressive treatment resulted in a probable B-cell dysfunction or depletion, resulting in a reduced potential to generate anti-SARS-CoV-2 antibodies. Key Exclusion criteria: • 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 hypersensitivity to treatment with immunoglobulins (WHO grade 3-4). • 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). Target number of patients: 86 patients (43 receive study treatment, 43 receive control treatment). Intervention: After randomization, one group (43 patients) receives treatment with Nanogam containing high titre neutralizing anti-SARS-CoV-2 antibodies (further referred to as Nanogam plus). The other group (43 patients) receives control treatment with Nanogam without high titre anti SARS-CoV-2 antibodies as control for Nanogam plus. Treatment is in a double blinded fashion. Main study endpoint severe course of disease, evaluated up until day 28 after randomization: • Start of adjunctive ventilator support (HFNO, mechanical ventilation) or an indication to do so but due to due to previously agreed treatment restrictions HFNO or mechanical ventilation is not initiated. • Admission to an intensive care unit for progression of respiratory insufficiency. • No clinical improvement on day 7 after randomization or any day thereafter after first day of treatment (based on oxygen use in patients that require oxygen and based on clinical disease burden (including fever) in patients that require no oxygen). • Readmission for COVID-19. Secondary endpoints To evaluate the impact of convalescent antibody-mediated treatment in the ICP population on: • Severity of COVID-19 disease in patients that have no anti SARS-CoV-2 antibodies upon inclusion (‘per protocol’ analysis). • Duration of hospitalization. • 28-day overall mortality • The four individual endpoints that compose the primary endpoint. • Time to complete recovery from COVID-19 related symptoms. • Rate of viral decay • Development of long-term persistent neutralizing antibodies against SARS-CoV-2 • T-cell immunity as measured by in vitro specific T cell response to COVID-19 tetrameric antigens.

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Projectnummer:
10430152110001
Looptijd: 100%
Looptijd: 100 %
2021
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. J. Heijmans
Verantwoordelijke organisatie:
Amsterdam UMC Locatie AMC