Anti COVID-19 Convalescent Plasma Therapy

Why is the research needed? The pandemic known as COVID-19 is now spreading across the world with currently (April 10, 2020) more than 1 115 530 active cases and 96 791 deaths. In most affected countries the current goal is to 'flatten the curve' of the epidemic since there is no health care system that is able to treat an extremely high volume of patients all at once. There is a need for immediately applicable treatments for the patients at highest risk, which gains time until targeted therapies become available. A key feature in the pathomechanism of the disease is that the virus elicits an immunological over-reaction in the human body termed 'cytokine storm'. In susceptible patients this hyper-inflammation itself is a significant burden and may even inhibit the body to generate antibodies against the virus in adequate quantities. Therefore, identifying the subset of patients with excess cytokine response and supplementing them with convalescent plasma from recovered donors may be a life-saving treatment option.

What is our study about? In light of recent promising data on plasma therapy in the treatment of COVID-19 and other viral epidemics, there is a need for better understanding the cytokine response to the virus in order to better characterize the target population for convalescent plasma therapy.

Our hypothesis is that convalescent plasma transfusion from healthy donors who recovered from SARS CoV-2 is able to reduce the cytokine storm in addition to replenish the patient's own antibodies in the acutely infected phase of the disease.

A plasmapheresis donation of 400ml will be performed in subjects who recovered from COVID-19 and who are otherwise eligible for plasma donation. The sample will be tested for anti-SARS CoV-2 neutralizing antibody titers and those that reach the level of 1:320 will be processed for transfusion at the Hungarian National Transfusion Service.

Recipients will be COVID-19 patients requiring hospitalization regardless of the severity of the disease or other co-morbidities. A blood-type matched transfusion of 200 ml convalescent plasma will be infused in a single sitting through an iv. infusion of 4 hours.

Recipients will be followed up at days 1, 3,7,12, 17, 28 for clinical symptoms, antibody levels and cytokine response.

Study Overview

• Status: Recruiting
• Conditions: COVID 19
• Intervention / Treatment: Biological: anti-SARS-CoV-2 convalescent plasma

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Eszter Fodor, medical doctor; Phone Number: +36306640494; Email: eszter.fodor@orthosera.com
• Study Contact Backup: Name: Zsombor Lacza, MD, PhD; Phone Number: +36305249554; Email: zsombor.lacza@orthosera.com

Study Locations

• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • Semmelweis University's Department of Pulmonology
    • Contact: Veronika Müller, MD; Phone Number: +3613559733
    • Principal Investigator: Veronika Muller, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria for blood donors :

• age : >18 and <60 years
• body weight : >50 kg
• confirmed previous SARS CoV-2 infection
• 2 negative SARS CoV-2 test result
• written informed consent
• neutralizing antibody titer min. 1 : 120

Exclusion criteria for blood donors :

• age : <18 or >60 years
• female subjects who are pregnant
• HIV1,2 hepatitis B,C or syphilis infection

to minimize the transfusional side effects our aim is to include mostly male donors.

Inclusion criteria for patients/recipients :

• age : >18 years
• admitted to hospital due to SARS CoV-2 infection
• written informed consent

Exclusion criteria for patients/recipients :

• age : <18 years
• female subjects who are pregnant or breastfeeding
• patients with prior allergic reaction to transfusion
• patients who received in the past 30 days immunoglobulin therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hospitalized patients with SARS CoV-2 infection	Biological: anti-SARS-CoV-2 convalescent plasma; Infusion of one unit of anti-SARS-CoV-2 convalescent plasma ~200 mL over 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing of viral load of SARS-CoV2	Copies of COVID-19 per ml	Day 1,3, 7, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in immunglobulin G COVID-19 antibody titer	Immunoglobulin G COVID-19 antibodies Immunglobulin G antibody titer	12 days
Changes at the cytokine pattern		12 days
Intensive Care Unit Admission	Proportion of patients with Intensive Care Unit Admission requirement	Day 7,12,28
Length of hospital stay	Days of Hospitalization	Day 7, 12, 28
Duration of mechanical ventilation	Days with mechanical ventilation	Day 7, 12, 28
Clinical Status	Clinical status assessed according to the World Health Organization guideline	Day 7, 12, 28
Mortality	Proportion of death patients at days	Day 7, 12, 28

Collaborators and Investigators

• Sponsor: Orthosera Kft.
• Collaborators: University of Pecs; Semmelweis University; Hungarian National Blood Service; Humán Bioplazma Kft - Kedrion
• Investigators: Principal Investigator: Veronika Müller, MD, PhD, Semmelweis University

Publications and helpful links

General Publications

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
• Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
• Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
• Belyakov IM, Hel Z, Kelsall B, Kuznetsov VA, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham PD, Clements JD, Franchini G, Strober W, Berzofsky JA. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat Med. 2001 Dec;7(12):1320-6. doi: 10.1038/nm1201-1320.
• Arabi Y, Balkhy H, Hajeer AH, Bouchama A, Hayden FG, Al-Omari A, Al-Hameed FM, Taha Y, Shindo N, Whitehead J, Merson L, AlJohani S, Al-Khairy K, Carson G, Luke TC, Hensley L, Al-Dawood A, Al-Qahtani S, Modjarrad K, Sadat M, Rohde G, Leport C, Fowler R. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus. 2015 Nov 19;4:709. doi: 10.1186/s40064-015-1490-9. eCollection 2015.
• Kardos D, Marschall B, Simon M, Hornyak I, Hinsenkamp A, Kuten O, Gyevnar Z, Erdelyi G, Bardos T, Paukovits TM, Magos K, Beres G, Szenthe K, Banati F, Szathmary S, Nehrer S, Lacza Z. Investigation of Cytokine Changes in Osteoarthritic Knee Joint Tissues in Response to Hyperacute Serum Treatment. Cells. 2019 Aug 3;8(8):824. doi: 10.3390/cells8080824.
• Nacsa J, Edghill-Smith Y, Tsai WP, Venzon D, Tryniszewska E, Hryniewicz A, Moniuszko M, Kinter A, Smith KA, Franchini G. Contrasting effects of low-dose IL-2 on vaccine-boosted simian immunodeficiency virus (SIV)-specific CD4+ and CD8+ T cells in macaques chronically infected with SIVmac251. J Immunol. 2005 Feb 15;174(4):1913-21. doi: 10.4049/jimmunol.174.4.1913.

Helpful Links

• 12. Ethics of using convalescent whole blood and convalescent plasma during the Ebola epidemic. Interim guidance for ethics review committees, researchers, national health authorities and blood transfusion services. 2015 WHO/HIS/KER/GHE/15.1

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: April 11, 2020
• First Submitted That Met QC Criteria: April 13, 2020
• First Posted (Actual): April 14, 2020

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; convalescent plasma; serum therapy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AntiCOVID19ORT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No