Convalescent Plasma as Treatment for Hospitalized Subjects With COVID-19 Infection

COVID-19 Clinical Trial

Official title:

Phase IIa Study Exploring the Safety and Efficacy of Convalescent Plasma From Recovered COVID-19 Donors Collected by Plasmapheresis as Treatment for Hospitalized Subjects With COVID-19 Infection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04343755
• Other study ID #: Pro2020-0375
• Status: Terminated
• Phase: Phase 2
• Start date: April 9, 2020
• Est. completion date: April 26, 2023

Study information

• Verified date: September 2023
• Source: Hackensack Meridian Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• This is a single arm phase IIa study of convalescent plasma for the treatment of individuals hospitalized with COVID-19 infection.

• Subjects will be considered as having completed the study after 60 (+/- 3) days, unless consent withdrawal or death occurs first.

• Interim analysis will be permitted as described in the statistical section 8.

• The final analysis will be conducted once the last subject completes the day 60 visit or withdraws from the study.

Description:

Overall study design

• This is a single arm phase IIa study of convalescent plasma for the treatment of individuals hospitalized with COVID-19 infection.

• Subjects will be considered as having completed the study after 60 (+/- 3) days, unless consent withdrawal or death occurs first.

• Interim analysis will be permitted as described in the statistical section 8.

• The final analysis will be conducted once the last subject completes the day 60 visit or withdraws from the study.

Number of subjects

• Up to 36 patients in track 2, and 19 patients in track 3 as described in the statistical section 8.

Overall study duration

• The study begins when the first subject (this will likely be a donor) signs the informed consent. The study will end once the last enrolled subject completes the study (likely a recipient).

• The expected duration of the study is approximately 12 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: April 26, 2023
• Est. primary completion date: April 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Donor Eligibility Criteria:

• Age 18-60

• A history of a positive nasopharyngeal swab for COVID-19 or a history of positive titer test.

• At least 14 days from resolution of COVID-19-associated symptoms including fevers

• One negative nasopharyngeal swabs for COVID-19 RNA

• Covid-19 neutralizing antibody >1:64

• Adequate venous access for apheresis

• Meets donor eligibility criteria in accordance to Hackensack University Medical Center (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at the JTCC, and all regulatory agencies as describes in SOP 800 01 (Appendix A)

• Required testing of the donor and product must be performed in accordance to FDA regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30)

Recipient Eligibility Criteria:

Recipients age >18 years old, are assigned to one of two clinical tracks, track 2 or 3, based on COVID-19 disease severity. Onset of first symptoms < 9 days.

Track 2:

• Hospitalized, moderate symptoms requiring medical care for COVID-19 infection

• Symptoms may include fever, dyspnea, dehydration among others

• Hypoxemia may be present but is not a requirement

Track 3:

• Requiring mechanical ventilation for the care of COVID-19 infection

• Requiring non-invasive positive pressure ventilation (NIPPV), such as continuous airway pressure (CPAP),bi-level positive airway pressure (BiPAP) or high flow nasal canula (HFNC).

Recipient exclusion criteria:

• History of severe transfusion reaction to plasma products

• Infusion of immune globulin within the previous 30 days

• AST or ALT > 10 x upper limit of normal

• Requirement for vasopressors

• COVID-19-associated acute kidney injury requiring dialysis

• DNR status

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Convalescent Plasma
Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection

Locations

Country	Name	City	State
United States	Hackensack University Medical Center	Hackensack	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Hackensack Meridian Health

Country where clinical trial is conducted

United States, 

References & Publications (19)

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. — View Citation

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. — View Citation

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. — View Citation

Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020 Apr 1;130(4):1545-1548. doi: 10.1172/JCI138003. No abstract available. — View Citation

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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. — View Citation

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. — View Citation

Gunn BM, Yu WH, Karim MM, Brannan JM, Herbert AS, Wec AZ, Halfmann PJ, Fusco ML, Schendel SL, Gangavarapu K, Krause T, Qiu X, He S, Das J, Suscovich TJ, Lai J, Chandran K, Zeitlin L, Crowe JE Jr, Lauffenburger D, Kawaoka Y, Kobinger GP, Andersen KG, Dye JM, Saphire EO, Alter G. A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus. Cell Host Microbe. 2018 Aug 8;24(2):221-233.e5. doi: 10.1016/j.chom.2018.07.009. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Tan M, Xiong X. Continuous and group sequential conditional probability ratio tests for phase II clinical trials. Stat Med. 1996 Oct 15;15(19):2037-51. doi: 10.1002/(SICI)1097-0258(19961015)15:193.0.CO;2-Z. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Hospitalized for COVID-19 But Not Intubated	Mechanical ventilation rate at 7 days from starting treatment in hospitalized COVID-19 patients	7 Days
Primary	Primary Objective for Patients With COVID-19 Already Intubated	Mortality rate at 30 days from starting treatment for patients with COVID-19	30 Days
Secondary	Duration of Hospitalization	The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death. Patients who are not discharged, are alive and still in the hospital on the date of closing follow-up, or lost follow-up on the date of closing follow-up will be considered censored on that date.	60 Days
Secondary	Duration of Mechanical Ventilation	The duration of mechanical ventilation is defined as the time in days from the first day of using mechanical ventilation to the last day of using mechanical ventilation. All evaluable patients will be included and no censoring for this analysis.	60 Days
Secondary	Time to Symptoms Resolution	The time to symptom resolution is defined as the time in days from new therapy initiation to the first documented symptom resolution as assessed by local site. Patients whose symptom are not resolved, who are dead, or lost follow-up on the designed follow-up date will be censored on that date.	60 Days
Secondary	Overall Survival	Overall survival rate at 60 days from starting treatment for patients with COVID-19	60 Days
Secondary	Rate of Virologic Clearance by Nasopharyngeal Swab at Day 10		10 Days
Secondary	Rate of Virologic Clearance by Nasopharyngeal Swab at Day 30		30 Days
Secondary	Impact of Donor Titers Level on Efficacy		60 Days
Secondary	Impact of Donor Titers Level on Safety		60 Days
Secondary	Recipient Anti-SARS-CoV2 Titer Assessment on Days 0 (Pre-infusion)		0 Days (pre-infusion)
Secondary	Recipient Anti-SARS-CoV2 Titer Assessment on Days 3		3 Days
Secondary	Recipient Anti-SARS-CoV2 Titer Assessment on Day 10		10 Days
Secondary	Recipient Anti-SARS-CoV2 Titer Assessment on Day 30		30 Days
Secondary	Recipient Anti-SARS-CoV2 Titer Assessment on Day 60		60 Days