Analysis of Coronavirus Disease 19 (COVID-19) Convalescent Plasma

• ClinicalTrials.gov Identifier: NCT04497779
• Recruitment Status: Active, not recruiting
• First Posted: August 4, 2020
• Last Update Posted: June 8, 2022
• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI); California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): City of Hope Medical Center

Study Description

Brief Summary:

Plasma from patients who have recovered from coronavirus disease 2019 (COVID-19) is referred to as COVID-19 convalescent plasma (CCP), and may contain antibodies against SARS-CoV-2, the virus responsible for COVID-19. CCP infusion is being evaluated as a therapeutic or prophylactic approach in COVID-19 patients. The goal of this study is to help develop a bank of convalescent plasma in California, especially in medically underserved communities particularly affected by the disease. In parallel, CCP administered to COVID-19 patients will be collected and analyzed to determine whether the antibody profile correlates with clinical outcome. The purpose of this non-therapeutic study is to learn more about the CCP antibody profile and the effect it may have in treating COVID-19 infection.

Condition or disease	Intervention/treatment
Asymptomatic COVID-19 Infection Laboratory-Confirmed; Symptomatic COVID-19 Infection Laboratory-Confirmed	Procedure: Biospecimen Collection; Other: Diagnostic Laboratory Biomarker Analysis; Other: Electronic Health Record Review; Other: Questionnaire Administration

Detailed Description:

PRIMARY OBJECTIVES:

I. Establish a testing service for screening prospective donors of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP).

II. Characterize the titer and neutralizing properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in CCP.

III. Correlate the SARS-CoV-2 antibody characteristics in CCP with the outcome in severely ill COVID-19 patients treated with CCP.

EXPLORATORY OBJECTIVES:

I. Facilitate the recruitment of CCP donors in medically underserved areas.

II. Develop high-throughput methods for detection/characterization of SARS-CoV-2 neutralizing and non-neutralizing antibodies.

III. Develop a bank of convalescent plasma that would be available for future studies relating to the content of CCP.

IV. Study the impact of antibody levels, donor characteristics and patient characteristics on outcome in COVID-19 patients treated with CCP.

V. Procure blood samples from COVID-19 convalescent volunteers for future COVID-19-related studies.

OUTLINE:

PROSPECTIVE CCP DONORS: Participants undergo collection of blood and/or nasopharyngeal swabs at the time of screening. Participants' medical records are reviewed.

CONVALESCENT BLOOD DONORS WHO CHOOSE NOT TO DONATE CCP: Participants undergo collection of blood sample at the time of screening. Participants' medical records are reviewed.

CCP RECIPIENTS: Patients undergo collection collection of blood samples at baseline, between CCP unit infusions, 24 hours after last CCP infusion, and between 14-28 after last CCP infusion. Patients' medical records are reviewed.

Study Design

• Study Type: Observational
• Actual Enrollment: 95 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Evaluation of Coronavirus Disease 19 (COVID-19) Convalescent Plasma
• Actual Study Start Date: July 13, 2020
• Estimated Primary Completion Date: November 21, 2022
• Estimated Study Completion Date: August 21, 2023

Groups and Cohorts

Group/Cohort

Intervention/treatment

Screening (biospecimen collection, medical record review, CCP); PROSPECTIVE CCP DONORS: Participants undergo collection of blood and/or nasopharyngeal swabs at the time of screening. Participants' medical records are reviewed. CONVALESCENT BLOOD DONORS WHO CHOOSE NOT TO DONATE CCP: Participants undergo collection of blood sample at the time of screening. Participants' medical records are reviewed. CCP RECIPIENTS: Patients undergo collection of blood samples at baseline, 12-24 hours after each CCP infusion, and 7 days after last CCP infusion. Patients' medical records are reviewed.

Procedure: Biospecimen Collection; Undergo collection of blood and/or nasopharyngeal swabs; Other: Diagnostic Laboratory Biomarker Analysis; Correlative studies; Other: Electronic Health Record Review; Donors and recipients have their medical records reviewed.; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures :

1. Convalescent plasma (CCP) units infused in coronavirus disease-2019 (COVID-19) patients [ Time Frame: Up to 12 months after enrollment ]
   Will be assayed for severe acute respiratory syndrome (SARS-CoV-2) immunoassay, coronavirus (CoV) PepSeq assay, and SARS-CoV-2 lenti-based neutralizing antibody titer.
2. All-cause mortality [ Time Frame: At day 28 post-CCP infusion ]
   Will naturally be compared to reported data from the other studies. Analysis will focus on demonstrating that the antibody content of donor plasma increases the odds of surviving past day 28. Will also develop a nomogram for the probability of success (alive at day 28), accounting for patient, donor material and donor antibody characteristics measurable covariates.
3. Donor antibody levels [ Time Frame: Up to 28 days post-CCP infusion ]
   Will be examined to see how this relates to the duration of hospitalization.

Secondary Outcome Measures :

1. Incidence of adverse events [ Time Frame: Up to 28 days post-CCP infusion ]
   Will be assessed on a 7-point ordinal scale, as recommended by the WHO patient outcome R&D Blueprint Group.
2. CCP recipient outcomes [ Time Frame: Up to 28 days post-CCP infusion ]

   Will be assessed on a 7-point ordinal scale. The scale is as follows:

   1. Death;
   2. Hospitalized, on invasive mechanical ventilation or ECMO;
   3. Hospitalized, on non-invasive ventilation or high flow oxygen devices;
   4. Hospitalized, requiring low flow supplemental oxygen;
   5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
   6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per protocol RDV administration);
   7. Not hospitalized

Other Outcome Measures:

1. Duration of hospitalization (days) [ Time Frame: Up to 28 days post-CCP infusion ]
   Patient can stay at the hospital for up to 28 days post-CCP infusion
2. Time to clinical improvement (days) [ Time Frame: Up to 28 days post-CCP infusion ]
   Will be assessed on a 7-point ordinal scale.

Biospecimen Retention:   Samples With DNA

Nasopharyngeal swab, blood samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosis of laboratory-confirmed COVID-19 infection

Criteria

For COVID-19 convalescent individuals:

• Age: ≥ 18 years
• Evidence of COVID-19 documented by a laboratory test either by: a diagnostic test (e.g., a NP swab) at the time of illness OR a positive serological test for SARS-CoV-2 antibodies after recovery, if prior diagnostic testing was not performed at the time COVID-19 was suspected.

Note: If volunteers can't provide evidence of COVID-19, but are otherwise eligible, then we will test them for SARS-CoV-2 antibodies to confirm eligibility.

• Be willing to complete a pre-screening questionnaire
• Be willing to donate blood samples
• Permit medical record review
• For prospective CCP donors only: weigh more than 110 pounds and be in general good health

For (COVID-19 convalescent plasma (CCP) recipients:

• Be enrolled in a clinical trial involving the infusion of CCP for the treatment of COVID-19.
• Be willing to provide blood samples
• Permit medical record review

Contacts and Locations

Locations

United States, California

City of Hope Medical Center

Duarte, California, United States, 91010

Sponsors and Collaborators

City of Hope Medical Center

National Cancer Institute (NCI)

California Institute for Regenerative Medicine (CIRM)

Investigators

• Principal Investigator: John Zaia; City of Hope Medical Center

More Information

Additional Information:

Website to register participants for the study 

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT04497779
• Other Study ID Numbers: 20204; NCI-2020-04000 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 20204 ( Other Identifier: City of Hope Medical Center ); P30CA033572 ( U.S. NIH Grant/Contract ); TGen ( Other Identifier: Translational Genomics Research Institute (TGen) )
• First Posted: August 4, 2020
• Last Update Posted: June 8, 2022
• Last Verified: September 2021

• 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

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Laboratory Infection; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Occupational Diseases