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

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

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV 2
• Intervention / Treatment: Biological: SARS-CoV-2 convalescent plasma; Biological: Plasma from a volunteer donor

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 Type: Interventional
• Enrollment (Actual): 1225
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Chinle, Arizona, United States, 86503
      • Center for American Indian Health - Chinle Office
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic, Phoenix
    • Tucson, Arizona, United States, 85719
      • University of Arizona, Phoenix
    • Tucson, Arizona, United States, 85724
      • University of Arizona, Tuscon
    • Whiteriver, Arizona, United States, 85941
      • Center for American Indian Health - Whiteriver Office
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Orange, California, United States, 92868
      • University of California, Irvine Health
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Western Connecticut Health Network, Danbury Hospital
    • Norwalk, Connecticut, United States, 06856
      • Western Connecticut Health Network, Norwalk Hospital
  • Florida
    • Coral Gables, Florida, United States, 33124
      • University of Miami
    • Miami, Florida, United States, 33136
      • University of Miami Clinical Translational Research Site
  • Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University Healthsystem
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center
    • Baltimore, Maryland, United States, 21205
      • The Johns Hopkins University
    • Hyattsville, Maryland, United States, 20782
      • MedStar Washington Hospital Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Worcester
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Wayne State University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Health Sciences Center
    • Gallup, New Mexico, United States, 87301
      • Center for American Indian Health - Gallup Office
    • Shiprock, New Mexico, United States, 87420
      • Center for American Indian Health - Shiprock Office
  • New York
    • Poughkeepsie, New York, United States, 12601
      • Vassar Brothers Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan/BrownUniversity (Rhode Island Hospital)
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • The University of Utah

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); United States Department of Defense; National Center for Advancing Translational Sciences (NCATS); State of Maryland; Bloomberg Foundation
• Investigators: Principal Investigator: David J Sullivan, MD, The Johns Hopkins University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Actual): January 14, 2022
• Study Completion (Actual): December 14, 2022

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19
• Other Study ID Numbers: IRB00247590; UL1TR003098 (U.S. NIH Grant/Contract); R01AI152078 (U.S. NIH Grant/Contract); W911QY2090012 (Other Grant/Funding Number: Department of Defense); U24TR001609 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: After publication of initial study manuscript
• IPD Sharing Access Criteria: Public
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No