Convalescent Plasma for Treatment of COVID-19 Patients With Pneumonia

NCT04374565 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 200114
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Corona Virus Infection; SARS-CoV 2; SARS Pneumonia; Pneumonia

Outcome Measures

Primary Outcomes (2)

• Number of Participants Transferred to Intensive Care Unit (ICU)

  Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.

  Days 0 - 60

• 28 Day Mortality

  Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.

  Days 0 - 28

Secondary Outcomes (14)

• Number of Participants With Serious Adverse Events

  Days 0 - 60

• Duration of SARS-CoV-2 Positivity

  Days 0 - 21

• Serum of Plasma Antibody Titer to SARS-CoV-2

  Day 28

• Cellular and Humoral Immune Response

  Day 28

• Supplemental Oxygen Free Days

  Days 0-28

Study Arms (1)

Study participants

EXPERIMENTAL

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.

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

Interventions

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

Study participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (2)

University of Virginia Medical Center

Charlottesville, Virginia, 22903, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (14)

• 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.

  PMID: 7578724 BACKGROUND

• 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.

  PMID: 15372080 BACKGROUND

• 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.

  PMID: 16121363 BACKGROUND

• 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.

  PMID: 27867062 BACKGROUND

• 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.

  PMID: 12967670 BACKGROUND

• 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.

  PMID: 7985997 BACKGROUND

• 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.

  PMID: 15616839 BACKGROUND

• 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.

  PMID: 16183666 BACKGROUND

• 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.

  PMID: 29923831 BACKGROUND

• 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.

  PMID: 27532807 BACKGROUND

• 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.

  PMID: 31826992 BACKGROUND

• 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.

  PMID: 25030060 BACKGROUND

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

  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.

  PMID: 11564809 BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections; Pneumonia

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Jeffrey Sturek
• Organization: University of Virginia

JMS3HK@hscmail.mcc.virginia.edu

434-284-1776

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pulmonary and Critical Care Medicine

Model Details: 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.

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: May 5, 2020
• Study Start: May 5, 2020
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: April 1, 2022
• Results First Posted: April 1, 2022

Record last verified: 2022-03

Locations

US (2)