Clinical trial NCT04429854: Donated Antibodies Working Against nCoV
Official title: A Randomized, Open-label, Adaptive, Proof-of-concept Clinical Trial of Donated Antibodies Working Against With COVID-19: DAWN-PLASMA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Federal Knowledge Centre (KCE)
First posted: 2020-06-12
Enrollment: 483
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 483 patients with 2:1 randomization. 320 patients receiving Convalescent Plasma - 163 patients receiving Standard of Care
Primary purpose: TREATMENT

Brief summary: This a phase II, proof-of-concept study. In the present study, we investigate if the administration of blood-plasma from patients recovered from COVID-19, could be effective to treat patients who are severely ill because of a COVID-19 infection. The general idea behind the transfusion, is that plasma of recovered patients contains antibodies that could eliminate the novel coronavirus causing COVID-19, and lead to a less severe course of the disease, or a faster healing. Simply put, in this study we would like to investigate whether 'borrowed immunity' from a person who has cured from this disease, could be applied to cure other patients more rapidly.

Detailed description: In December 2019, a new coronavirus (the SARS-CoV-2 virus) emerged, which spread fast across the world, and has led to a pandemic. The disease caused by this virus, called COVID-19, has a mild course in a high number of infected people, but is known to have a more severe course in some. Currently, there are no successful treatments with a known effect on the course of the disease in patients suffering from COVID-19. In this study, we will examine whether plasma, a treatment that has been used in human subjects for other diseases (and is known to be safe), can be used to influence the course of COVID-19 towards a lower severity.

The aim of the study is to evaluate clinical efficacy and safety of convalescent plasma for COVID-19.

This clinical trial is an adaptive, randomized, open-label phase II proof-of-concept study to investigate the safety and effect of potentially interesting treatments, for the treatment of hospitalized adult patients suffering from COVID-19.

Because an active treatment for COVID-19 is lacking, plasma donation is now being proposed. To investigate this effect of plasma, we will compare two groups of patients. One group will get standard treatment, plus plasma from a patient recently cured from COVID-19. A second group will get standard treatment alone. In this study, 2 patients out of 3 will receive plasma, and 1 patient out of 3 will receive standard treatment alone. After the study, we will be able to establish whether plasma donation is useful or not.

Eligibility criteria: Inclusion Criteria:

1. Subject (≥18 years old) or legally authorized representative provides informed consent prior to initiation of any study procedures.
2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
3. Male or non-pregnant female adult ≥18 years of age at time of enrolment.
4. Patient should be hospitalized
5. Has a confirmed diagnosis of SARS-CoV-2 infection, defined as either:

   1. laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen as diagnosed within 60 hours prior to randomization or
   2. The combination of upper or lower respiratory infection symptoms (fever, cough, dyspnea, desaturation) and typical findings on chest CT scan and absence of other plausible diagnoses
6. Illness of any duration, and at least one of the following:

   1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or
   2. Clinical assessment (evidence of rales/crackles on exam) AND SpO2 ≤ 94% on room air, or
   3. Requiring supplemental oxygen.
7. ABO D typing of the patient should be done at least once and the result should be known.

Exclusion Criteria:

1. Receiving invasive (any mode where a patient has been intubated endotracheally, or via tracheostomy) or non-invasive (for instance, but not restricted to CPAP, PSV, PCV, SiMV) mechanical ventilation before or upon randomization.
2. Pregnancy or breast feeding.
3. Any medical condition which would impose an unacceptable safety hazard by participation to the study.
4. Patients with a documented grade 3 allergic reaction after the administration of fresh frozen plasma (i.e. systemic reaction with cardiovascular and/or respiratory involvement)
5. Patients that have treatment restriction that excludes mechanical ventilation and/or endotracheal intubation
6. Rituximab or another anti-CD20 monoclonal antibody (f.ex. obinutuzumab) has been administered during the year prior of the date of admission.

Primary outcomes:
measure: Patients requiring mechanical ventilation or death
timeFrame: No mechanical ventilation at day 15 after hospitalization.
Secondary outcomes:
measure: Clinical status of subject at day 15 and day 30 (on a 10-point "WHO progression" ordinal scale)
timeFrame: day 15 and day 30
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: ZNA
city: Bonheiden
country: Belgium
facility: Imelda Ziekenhuis Bonheiden
city: Brussel
country: Belgium
facility: Institut Bordet
city: Brussel
country: Belgium
facility: UMC Sint-Pieter
city: Brussel
country: Belgium
facility: CHU Brugmann
city: Brussel
country: Belgium
facility: Erasmus Ziekenhuis
city: Brussel
country: Belgium
facility: UZ Brussel
city: Brussel
country: Belgium
facility: Cliniques Universitaires St Luc
city: Deinze
country: Belgium
facility: AZ Sint-Vincentius
city: Gent
country: Belgium
facility: AZ Maria Middelares
city: Gent
country: Belgium
facility: AZ Sint-Lucas
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHC Liège Mont Légia
city: Liège
country: Belgium
facility: CHR Citadelle Liège
city: Liège
country: Belgium
facility: CHU Liège Sart-Tilman
city: Mons
country: Belgium
facility: CHU Ambroise Paré
city: Mons
country: Belgium
facility: CHR Jolimont Mons-Hainaut
city: Roeselare
country: Belgium
facility: AZ Delta
city: Sint-Truiden
country: Belgium
facility: Sint-Trudo Ziekenhuis
city: Tournai
country: Belgium
facility: Centre Hospitalier de Wallonie Picarde (CHwapi)
Study officials:
affiliation: UZ Leuven
name: Geert Meyfroidt, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Devos T, Geukens T, Schauwvlieghe A, Arien KK, Barbezange C, Cleeren M, Compernolle V, Dauby N, Desmecht D, Grimaldi D, Lambrecht BN, Luyten A, Maes P, Moutschen M, Romano M, Seyler L, Nevessignsky MT, Vandenberghe K, van Griensven J, Verbeke G, Vlieghe E, Yombi JC, Liesenborghs L, Verhamme P, Meyfroidt G. A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial. Trials. 2020 Nov 27;21(1):981. doi: 10.1186/s13063-020-04876-0.