Convalescent Plasma to Limit SARS-CoV-2 Associated Complications (CSSC-004)

• ClinicalTrials.gov Identifier: NCT04373460
• Recruitment Status: Completed
• First Posted: May 4, 2020
• Results First Posted: January 31, 2023
• Last Update Posted: June 2, 2023
• Sponsor: Johns Hopkins University
• Collaborators: State of Maryland; Bloomberg Foundation; United States Department of Defense; National Institute of Allergy and Infectious Diseases (NIAID); National Center for Advancing Translational Sciences (NCATS)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

To assess the efficacy and safety of Human coronavirus immune plasma (HCIP) to reduce the risk of hospitalization or death, the duration of symptoms and duration of nasopharyngeal or oropharyngeal viral shedding.

Condition or disease	Intervention/treatment	Phase
SARS-CoV 2	Biological: SARS-CoV-2 convalescent plasma; Biological: Plasma from a volunteer donor	Phase 2

Detailed Description:

The purpose of this randomized, double-blind, controlled, phase 2 trial is to evaluate the efficacy of treatment with HCIP in reducing hospitalization and death prior to hospitalization among outpatient adults who have RNA detection test-confirmed COVID-19 AND have developed any symptoms of COVID-19 including but not limited to fever, cough, or other COVID associated symptoms like anosmia. Ambulatory/outpatient adults subjects 18 years of age or older, regardless of risk factors for severe illness may participate. A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A total of approximately 1344 eligible subjects stratified with a target goal (but not binding) of 50:50 in the <65 vs ≥ 65 age range will be randomized in a 1:1 ratio to receive either HCIP or control plasma.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Comparison of the Efficacy and Safety of Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune) Plasma Among Outpatients With Symptomatic COVID-19
• Actual Study Start Date: June 3, 2020
• Actual Primary Completion Date: January 14, 2022
• Actual Study Completion Date: December 14, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: SARS-CoV-2 convalescent plasma; SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma.	Biological: SARS-CoV-2 convalescent plasma; SARS-CoV-2 convalescent plasma (1 cup; minimum of 175 mL collected by apheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320 and after July 2021 meets FDA criteria for high titer plasma.; Other Name: Human coronavirus immune plasma (HCIP)
Active Comparator: Standard Control plasma; Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative.	Biological: Plasma from a volunteer donor; Plasma collected from a volunteer donor prior to January 1, 2020 will not be tested for SARS-CoV-2 antibodies. Plasma collected after December 31, 2019 will be confirmed as SARS-CoV-2 seronegative.

Outcome Measures

Primary Outcome Measures :

1. Cumulative Number of Hospitalizations or Deaths Prior to Hospitalization [ Time Frame: Up to day 28 ]
   Cumulative Number measured as the proportion of subjects who were hospitalized or who died prior to hospitalization
2. Cumulative Incidence of Severe Infusion Reactions [ Time Frame: Up to day 28 ]
   Cumulative incidence measured as rate per person-years experiencing treatment-related severe infusion reactions during the study period.
3. Cumulative Incidence of Treatment-related Grade 3 or Higher Adverse Events [ Time Frame: Up to day 90 ]
   Cumulative incidence measured as rate per person-years experiencing a Grade 3 or higher.
4. Cumulative Incidence of Treatment-related Acute Respiratory Distress Syndrome (ARDS) [ Time Frame: Up to day 28 ]
   Cumulative incidence measured as rate per person-years of treatment-related severe Acute Respiratory Distress Syndrome (ARDS) during the study period.

Secondary Outcome Measures :

1. Serum SARS-CoV-2 Antibody Titers by Visit [ Time Frame: Days 0, 14, 28 and 90 ]
   Geometric mean Spike Receptor Binding Domain (RBD) titers at day 0, 14, 28 and 90 between the randomized arms.

Other Outcome Measures:

1. Number of Participants With ICU Admission [ Time Frame: Up to day 90 ]
   Disease severity measured by admission to the ICU
2. Number of Participants With Invasive Mechanical Ventilation [ Time Frame: Up to day 90 ]
   Disease severity measured by invasive mechanical ventilation
3. Number of Participants Who Died [ Time Frame: Up to day 90 ]
   Disease severity measured by death
4. Number of Participants With Resolved COVID-19 Symptoms at Day 14 [ Time Frame: Day 14 ]
   Number of participants with resolved COVID-19 symptoms at day 14
5. Number of Participants With Resolved COVID-19 Symptoms at Day 28 [ Time Frame: Day 28 ]
   Number of participants with resolved COVID-19 symptoms at day 28
6. Number of Participants With Resolved COVID-19 Symptoms at Day 90 [ Time Frame: Day 90 ]
   Number of participants with resolved COVID-19 symptoms at day 90
7. Impact of Convalescent Plasma on Outcome as Assessed by Change in Hospitalization Rate [ Time Frame: Day 0 to Day 90 ]
   Assess change in hospitalization rate as measured by number of hospitalizations stratified by age groups <65 and >=65
8. Impact of Donor Antibody Titers on Hospitalization Rate of Convalescent Plasma Recipients [ Time Frame: Day 0 to Day28 ]
   Impact of donor antibody titers (high/low) will be assessed by hospitalization rate as measured by number of hospitalizations.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• ≥ 18 years of age
• Competent and capable to provide informed consent
• • Positive molecular test for presence of SARS-CoV-2 in fluid collected by saliva for antigen, oropharyngeal or nasopharyngeal swab
• Experiencing any symptoms of COVID-19 including but not limited to fever(T> 100.5º F), cough, or other COVID associated symptoms like anosmia
• ≤ 8 days since the first symptoms of COVID-19
• ≤ 8 days since first positive SARS-CoV-2 RNA test
• Able and willing to comply with protocol requirements listed in the informed consent

Exclusion Criteria:

• Hospitalized or expected to be hospitalized within 24 hours of enrollment
• Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance
• History of prior reactions to transfusion blood products
• Inability to complete therapy with the study product within 24 hours after enrollment
• Receiving any treatment drug for COVID-19 within 14 days prior to screening evaluation (monoclonal antibodies, compassionate use or study trial related). Steroid treatment at any time does not affect study eligibility

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Arizona

Center for American Indian Health - Chinle Office

Chinle, Arizona, United States, 86503

Mayo Clinic, Phoenix

Phoenix, Arizona, United States, 85054

University of Arizona, Phoenix

Tucson, Arizona, United States, 85719

University of Arizona, Tuscon

Tucson, Arizona, United States, 85724

Center for American Indian Health - Whiteriver Office

Whiteriver, Arizona, United States, 85941

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095

University of California, Irvine Health

Orange, California, United States, 92868

United States, Connecticut

Western Connecticut Health Network, Danbury Hospital

Danbury, Connecticut, United States, 06810

Western Connecticut Health Network, Norwalk Hospital

Norwalk, Connecticut, United States, 06856

United States, Florida

University of Miami

Coral Gables, Florida, United States, 33124

University of Miami Clinical Translational Research Site

Miami, Florida, United States, 33136

United States, Illinois

NorthShore University HealthSystem

Evanston, Illinois, United States, 60201

United States, Louisiana

Tulane University

New Orleans, Louisiana, United States, 70112

United States, Maryland

Anne Arundel Medical Center

Annapolis, Maryland, United States, 21401

The Johns Hopkins University

Baltimore, Maryland, United States, 21205

MedStar Washington Hospital Center

Hyattsville, Maryland, United States, 20782

United States, Massachusetts

University of Massachusetts Worcester

Worcester, Massachusetts, United States, 01655

United States, Michigan

Wayne State University

Detroit, Michigan, United States, 48202

United States, New Mexico

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, United States, 87131

Center for American Indian Health - Gallup Office

Gallup, New Mexico, United States, 87301

Center for American Indian Health - Shiprock Office

Shiprock, New Mexico, United States, 87420

United States, New York

Vassar Brothers Medical Center

Poughkeepsie, New York, United States, 12601

University of Rochester

Rochester, New York, United States, 14642

United States, Ohio

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45219

United States, Rhode Island

Lifespan/BrownUniversity (Rhode Island Hospital)

Providence, Rhode Island, United States, 02903

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

United States, Utah

The University of Utah

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

Johns Hopkins University

State of Maryland

Bloomberg Foundation

United States Department of Defense

National Institute of Allergy and Infectious Diseases (NIAID)

National Center for Advancing Translational Sciences (NCATS)

Investigators

• Principal Investigator: David J Sullivan, MD; The Johns Hopkins University

  Study Documents (Full-Text)

Documents provided by Johns Hopkins University:

Study Protocol  [PDF] November 4, 2021

Statistical Analysis Plan  [PDF] November 2, 2021

Informed Consent Form  [PDF] July 21, 2021

More Information

Publications of Results:

Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, Heath SL, Levine AC, Meisenberg BR, Spivak ES, Anjan S, Huaman MA, Blair JE, Currier JS, Paxton JH, Gerber JM, Petrini JR, Broderick PB, Rausch W, Cordisco ME, Hammel J, Greenblatt B, Cluzet VC, Cruser D, Oei K, Abinante M, Hammitt LL, Sutcliffe CG, Forthal DN, Zand MS, Cachay ER, Raval JS, Kassaye SG, Foster EC, Roth M, Marshall CE, Yarava A, Lane K, McBee NA, Gawad AL, Karlen N, Singh A, Ford DE, Jabs DA, Appel LJ, Shade DM, Ehrhardt S, Baksh SN, Laeyendecker O, Pekosz A, Klein SL, Casadevall A, Tobian AAR, Hanley DF. Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma. medRxiv. 2021 Dec 21:2021.12.10.21267485. doi: 10.1101/2021.12.10.21267485. Preprint.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sullivan DJ, Gebo KA, Shoham S, Bloch EM, Lau B, Shenoy AG, Mosnaim GS, Gniadek TJ, Fukuta Y, Patel B, Heath SL, Levine AC, Meisenberg BR, Spivak ES, Anjan S, Huaman MA, Blair JE, Currier JS, Paxton JH, Gerber JM, Petrini JR, Broderick PB, Rausch W, Cordisco ME, Hammel J, Greenblatt B, Cluzet VC, Cruser D, Oei K, Abinante M, Hammitt LL, Sutcliffe CG, Forthal DN, Zand MS, Cachay ER, Raval JS, Kassaye SG, Foster EC, Roth M, Marshall CE, Yarava A, Lane K, McBee NA, Gawad AL, Karlen N, Singh A, Ford DE, Jabs DA, Appel LJ, Shade DM, Ehrhardt S, Baksh SN, Laeyendecker O, Pekosz A, Klein SL, Casadevall A, Tobian AAR, Hanley DF. Early Outpatient Treatment for Covid-19 with Convalescent Plasma. N Engl J Med. 2022 May 5;386(18):1700-1711. doi: 10.1056/NEJMoa2119657. Epub 2022 Mar 30.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04373460
• Other Study ID Numbers: IRB00247590; R01AI152078 ( U.S. NIH Grant/Contract ); W911QY2090012 ( Other Grant/Funding Number: Department of Defense ); U24TR001609 ( U.S. NIH Grant/Contract ); UL1TR003098 ( U.S. NIH Grant/Contract )
• First Posted: May 4, 2020
• Results First Posted: January 31, 2023
• Last Update Posted: June 2, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual participant data (IPD) collected in this study, including data dictionaries, will be made available to other researchers after the end of the study.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: After publication of initial study manuscript
• Access Criteria: Public

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins University:

COVID-19