Convalescent Plasma for Treatment of COVID-19 Patients With Pneumonia

NCT ID: NCT04374565

Last Updated: 2022-04-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-05

Study Completion Date

2021-03-05

Brief Summary

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This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.

Detailed Description

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There are no proven treatments for coronavirus disease (COVID-19) and associated pneumonia caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Recent experience in China suggests that convalescent immune plasma(CIP)may be an effective treatment for COVID-19. In the pandemic situation where there are no vaccines for COVID-19, specific antibodies in convalescent plasma induced by infection may provide passive protective immunity. Passive antibody therapy was the first immunotherapy dating back to the 1890's for the treatment of infectious diseases before the development of antibiotics 1940's. Experience from prior outbreaks with other coronaviruses, such as SARS-CoV-1 shows that such convalescent plasma contains neutralizing antibodies to the relevant virus. In SARS-CoV-2, passive antibody therapy from CIP probably provided protection by viral neutralization. CIP was also used in the 2013 Ebola epidemic. A small non-randomized study in Sierra Leone revealed a significant increase in survival for who received CIP4. CIP administration is the only approach that provides immediate immunity to patients who have been exposed or who have active disease.

This approach is immediately available from individuals who have recovered, are viral free,and can donate immune plasma (IP) containing high titer neutralizing antibodies. Passive antibody therapy can be given to a patient recently exposed or a patient who is developing an infection with COVID-19 by obtaining plasma units from immune individuals by standard plasmapheresis using FDA-approved blood banking procedures, cross matching the unit(s) to the recipients and infusing the unit(s) using standard transfusion procedures for blood products. Based on the safety and long-term experience with plasma infusions, plasma exchanges, and other procedures involving plasma or plasma product, this protocol was designed as a phase II single arm trial that involves the administration of antibodies to a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease due to that agent.

The only antibody formulation that is available for emergent use is that found in convalescent plasma. As more individuals contract COVID-19 and recover, the number of potential donors will increase.

The principle of passive antibody therapy is that it is more effective when used for prophylaxis than for treatment of disease. When used for therapy, antibody is most effective when administered shortly after the onset of symptoms. The reason for temporal variation in efficacy is not well understood but could reflect that passive antibody works by neutralizing the initial inoculum, which is likely to be much smaller than that of established disease. Alternatively, antibodies may dampen the early inflammatory response leaving the infected individual asymptomatic. For example, antibody therapy for pneumococcal pneumonia was most effective when given shortly after the onset of symptoms and was of no benefit if antibody therapy was delayed beyond the third day of disease. For passive antibody therapy to be effective, a sufficient amount of antibody must be infused. The antibody will circulate in the blood, reach tissues,and provide protection against infection. Depending on the type of antibody, amount, and composition, the half-life can vary from weeks to months. It is under these circumstances, the investigators plan to treat patients who are sick enough to be hospitalized before the onset of overwhelming disease involving a systemic inflammatory response, sepsis, and/or ARDS.

Conditions

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Corona Virus Infection SARS-CoV 2 SARS Pneumonia Pneumonia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is a single arm phase II trial to assess preliminary efficacy and confirm safety of infusions of antiSARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms with or without confirmed interstitial COVID-19 pneumonia by CXR or chest CT. A total of 29 eligible subjects will be enrolled to receive high titer anti-SARS-CoV-2 plasma. Participants will be compared to a historical control group via retrospective chart review.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Study participants

A total of 29 eligible subjects will be enrolled to receive high titer anti-SARS-CoV-2 plasma. Participants will be compared to a historical control group via retrospective chart review.

Group Type EXPERIMENTAL

High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma

Intervention Type DRUG

Pathogen reduced SARS-CoV-2 convalescent plasma (1-2 units; \~200 mL each for a total of 200-400mls) given preferably in one day, but allowable to be given over 2 days if clinical circumstances delay infusions in 1 day), with titer to be determined after the unit has been infused.

Interventions

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High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma

Pathogen reduced SARS-CoV-2 convalescent plasma (1-2 units; \~200 mL each for a total of 200-400mls) given preferably in one day, but allowable to be given over 2 days if clinical circumstances delay infusions in 1 day), with titer to be determined after the unit has been infused.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients must be 18 years of age or older
* Patients hospitalized with COVID-19 respiratory symptoms within 72 hours of admission to a"floor" bed (non-ICU bed) and confirmation via SARS-CoV-2 RT-PCR testing.
* Patient and/or surrogate is willing and able to provide written informed consent and comply with all protocol requirements.
* Patients with hematologic malignancies or solid tumors are eligible.
* Patients with autoimmune disorders are eligible.
* Patients with immunodeficiency and organ or stem cell transplant recipients are eligible.
* Patients who have received or are receiving hydroxychloroquine or chloroquine are eligible (but will be taken off the drug)
* Prior use of IVIG is allowed but the investigator should consider the potential for a hypercoagulable state.

Exclusion Criteria

* Patients requiring mechanical ventilation or \>6 liters per minute nasal cannula oxygen
* Patients on other anti-COVID-19 trials being treated with tocilizumab (anti-IL-6 receptor), Siltuximab (anti-IL-2), Remdesivir, or other pharmacological trials that may be initiated hereafter.
* A pre-existing condition or use of a medication that, in the opinion of the site investigator, may place the individual at a substantially increased risk of thrombosis (e.g., cryoglobulinemia, severe refractory hypertriglyceridemia, or clinically significant monoclonal gammopathy).
* Contraindication to transfusion or history of prior reactions to transfusion blood products.
* Medical conditions for which receipt of 500-600 mL of intravenous fluid may be dangerous to the subject (e.g., decompensated congestive heart failure).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Jeffrey Sturek, MD, PhD

Assistant Professor of Pulmonary and Critical Care Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Virginia Medical Center

Charlottesville, Virginia, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Countries

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United States

References

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Casadevall A, Scharff MD. Return to the past: the case for antibody-based therapies in infectious diseases. Clin Infect Dis. 1995 Jul;21(1):150-61. doi: 10.1093/clinids/21.1.150.

Reference Type BACKGROUND
PMID: 7578724 (View on PubMed)

Casadevall A, Dadachova E, Pirofski LA. Passive antibody therapy for infectious diseases. Nat Rev Microbiol. 2004 Sep;2(9):695-703. doi: 10.1038/nrmicro974.

Reference Type BACKGROUND
PMID: 15372080 (View on PubMed)

Zhang JS, Chen JT, Liu YX, Zhang ZS, Gao H, Liu Y, Wang X, Ning Y, Liu YF, Gao Q, Xu JG, Qin C, Dong XP, Yin WD. A serological survey on neutralizing antibody titer of SARS convalescent sera. J Med Virol. 2005 Oct;77(2):147-50. doi: 10.1002/jmv.20431.

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Sahr F, Ansumana R, Massaquoi TA, Idriss BR, Sesay FR, Lamin JM, Baker S, Nicol S, Conton B, Johnson W, Abiri OT, Kargbo O, Kamara P, Goba A, Russell JB, Gevao SM. Evaluation of convalescent whole blood for treating Ebola Virus Disease in Freetown, Sierra Leone. J Infect. 2017 Mar;74(3):302-309. doi: 10.1016/j.jinf.2016.11.009. Epub 2016 Nov 17.

Reference Type BACKGROUND
PMID: 27867062 (View on PubMed)

Casadevall A, Pirofski LA. Antibody-mediated regulation of cellular immunity and the inflammatory response. Trends Immunol. 2003 Sep;24(9):474-8. doi: 10.1016/s1471-4906(03)00228-x. No abstract available.

Reference Type BACKGROUND
PMID: 12967670 (View on PubMed)

Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother. 1994 Aug;38(8):1695-702. doi: 10.1128/AAC.38.8.1695. No abstract available.

Reference Type BACKGROUND
PMID: 7985997 (View on PubMed)

Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.

Reference Type BACKGROUND
PMID: 15616839 (View on PubMed)

Yeh KM, Chiueh TS, Siu LK, Lin JC, Chan PK, Peng MY, Wan HL, Chen JH, Hu BS, Perng CL, Lu JJ, Chang FY. Experience of using convalescent plasma for severe acute respiratory syndrome among healthcare workers in a Taiwan hospital. J Antimicrob Chemother. 2005 Nov;56(5):919-22. doi: 10.1093/jac/dki346. Epub 2005 Sep 23.

Reference Type BACKGROUND
PMID: 16183666 (View on PubMed)

Ko JH, Seok H, Cho SY, Ha YE, Baek JY, Kim SH, Kim YJ, Park JK, Chung CR, Kang ES, Cho D, Muller MA, Drosten C, Kang CI, Chung DR, Song JH, Peck KR. Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience. Antivir Ther. 2018;23(7):617-622. doi: 10.3851/IMP3243. Epub 2018 Jun 20.

Reference Type BACKGROUND
PMID: 29923831 (View on PubMed)

Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, Al-Dawood A, Al-Qahtani S, Al-Omari A, Al-Hameed F, Hayden FG, Fowler R, Bouchama A, Shindo N, Al-Khairy K, Carson G, Taha Y, Sadat M, Alahmadi M. Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia. Emerg Infect Dis. 2016 Sep;22(9):1554-61. doi: 10.3201/eid2209.151164.

Reference Type BACKGROUND
PMID: 27532807 (View on PubMed)

Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J, Shi Z, Zhou Y, Du L, Li F. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry. J Virol. 2020 Feb 14;94(5):e02015-19. doi: 10.1128/JVI.02015-19. Print 2020 Feb 14.

Reference Type BACKGROUND
PMID: 31826992 (View on PubMed)

Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.

Reference Type BACKGROUND
PMID: 25030060 (View on PubMed)

China puts 245 COVID-19 patients on convalescent plasma therapy. In: Huaxia, (ed): XinhuaNet, 2020.

Reference Type BACKGROUND

Crowe JE Jr, Firestone CY, Murphy BR. Passively acquired antibodies suppress humoral but not cell-mediated immunity in mice immunized with live attenuated respiratory syncytial virus vaccines. J Immunol. 2001 Oct 1;167(7):3910-8. doi: 10.4049/jimmunol.167.7.3910.

Reference Type BACKGROUND
PMID: 11564809 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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200114

Identifier Type: -

Identifier Source: org_study_id

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