Donated Antibodies Working Against nCoV (DAWN-Plasma)

• ClinicalTrials.gov Identifier: NCT04429854
• Recruitment Status: Recruiting
• First Posted: June 12, 2020
• Last Update Posted: June 12, 2020
• Sponsor: Universitaire Ziekenhuizen Leuven
• Collaborator: Federal Knowledge Centre (KCE)
• Information provided by (Responsible Party): Universitaire Ziekenhuizen Leuven

Study Description

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Biological: Convalescent Plasma; Drug: Standard of care	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 483 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 483 patients with 2:1 randomization. 322 patients receiving Convalescent Plasma - 161 patients receiving Standard of Care
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Adaptive, Proof-of-concept Clinical Trial of Donated Antibodies Working Against With COVID-19: DAWN-PLASMA
• Actual Study Start Date: May 2, 2020
• Estimated Primary Completion Date: November 2, 2021
• Estimated Study Completion Date: November 2, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Convalescent Plasma; 4 units of convalescent plasma: 2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible; 2 units of plasma should be administered between 24h and 36h after the first infusion	Biological: Convalescent Plasma; 4 units of convalescent plasma: 2 units of plasma are administered within 12h after randomization, but preferably as soon as practically possible; 2 units of plasma should be administered between 24h and 36h after the first infusion Other investigational products may be added as part of the adaptive study design.; Drug: Standard of care; Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.
Standard of Care; Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive. Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.	Drug: Standard of care; Since there are no current approved treatment options for COVID-19, the standard of care is mostly supportive.

Outcome Measures

Primary Outcome Measures :

1. Patients requiring mechanical ventilation or death [ Time Frame: No mechanical ventilation at day 15 after hospitalization. ]
   Primary outcome of the study is the number of patients alive without mechanical ventilation at day 15 after hospitalization.

Secondary Outcome Measures :

1. Clinical status of subject at day 15 and day 30 (on a 10-point "WHO progression" ordinal scale) [ Time Frame: day 15 and day 30 ]

   0. Uninfected. Non viral RNA detected

   1. Ambulatory, Asymptomatic, viral RNA detected
   2. Ambulatory, Symptomatic, Independent
   3. Ambulatory, Symptomatic, Assistance needed
   4. Hospitalized, mild disease, No oxygen therapy needed
   5. Hospitalized, mild disease, Oxygen by mask of nasal prongs
   6. Hospitalized, severe disease, Oxygen by NIV or High flow
   7. Hospitalized, severe disease, Intubation and mechanical ventilation (pO2/FiO2>=150 OR SpO2/FIO2>=200)
   8. Hospitalized, severe disease, Mechanical ventilation (pO2/FiO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min)
   9. Hospitalized, severe disease, Mechanical ventilation pO2/FiO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO
   10. Death, Dead

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Geert Meyfroidt, MD, PhD; 003216332211; geert.meyfroidt@uzleuven.be

Locations

Belgium

ZNA; Recruiting

Antwerpen, Belgium, 2050

Contact: Niels Van Regenmortel, MD niels.vanregenmortel@zna.be

Institut Bordet; Not yet recruiting

Brussel, Belgium, 1000

Contact: Georgala Aspasia, MD aspasia.georgala@bordet.be

UMC Sint-Pieter; Recruiting

Brussel, Belgium, 1000

Contact: Nicolas Dauby, MD ndauby@ulb.ac.be

CHU Brugmann; Active, not recruiting

Brussel, Belgium, 1030

Erasmus Ziekenhuis; Active, not recruiting

Brussel, Belgium, 1070

UZ Brussel; Recruiting

Brussel, Belgium, 1090

Contact: Lucie Seyler, MD Lucie.Seyler@uzbrussel.be

Cliniques Universitaires St Luc; Recruiting

Brussel, Belgium, 1200

Contact: Jean Yombi, MD jean.yombi@uclouvain.be

AZ Groeninge; Recruiting

Kortrijk, Belgium, 8500

Contact: Matthias Leys, MD mathias.leys@azgroeninge.be

UZ Leuven; Recruiting

Leuven, Belgium, 3000

Contact: Timothy Devos, MD,PHD timothy.devos@uzleuven.be

CHC Liège Mont Légia; Recruiting

Liège, Belgium, 4000

Contact: Laurent Jadot, MD Laurent.Jadot@CHC.be

CHR Citadelle Liège; Active, not recruiting

Liège, Belgium, 4000

CHU Liège Sart-Tilman; Recruiting

Liège, Belgium, 4000

Contact: Michel Moutschen, MD mmoutschen@chuliege.be

CHR Jolimont Mons-Hainaut; Recruiting

Mons, Belgium, 7100

Contact: Clotilde Visée, MD Clotilde.VISEE@jolimont.be

AZ Delta; Recruiting

Roeselare, Belgium, 8800

Contact: Bernard Bouckaert, MD bernard.bouckaert@azdelta.be

Sponsors and Collaborators

Universitaire Ziekenhuizen Leuven

Federal Knowledge Centre (KCE)

Investigators

• Study Director: Geert Meyfroidt, MD, PhD; UZ Leuven

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Devos T, Geukens T, Schauwvlieghe A, Ariën 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. Erratum in: Trials. 2020 Dec 14;21(1):1024.

• Responsible Party: Universitaire Ziekenhuizen Leuven
• ClinicalTrials.gov Identifier: NCT04429854
• Other Study ID Numbers: S63992
• First Posted: June 12, 2020
• Last Update Posted: June 12, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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