Convalescent Plasma to Stem Coronavirus (CSSC-001) (CSSC-001)

• ClinicalTrials.gov Identifier: NCT04323800
• Recruitment Status: Completed
• First Posted: March 27, 2020
• Results First Posted: April 22, 2022
• Last Update Posted: April 26, 2022
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: March 24, 2020
• First Posted Date: March 27, 2020
• Results First Submitted Date: April 20, 2022
• Results First Posted Date: April 22, 2022
• Last Update Posted Date: April 26, 2022
• Actual Study Start Date: June 10, 2020
• Actual Primary Completion Date: April 22, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 22, 2022)

• Efficacy of Treatment at Day 28 as Assessed by Number of Participants Who Develop SARS-Cov-2 Infection [ Time Frame: Day 28 ]
  Comparison of proportions of cumulative incidence of development of SARS-Cov-2 infection (symptoms compatible with infection and/or + molecular testing) regardless of disease severity, following high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to COVID-19.
• Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Number of Participants With "Serious Adverse Events" [ Time Frame: Up to Day 28 ]
  Number of participants with serious adverse events categorized as either severe infusion reactions or Acute Respiratory Distress Syndrome during the study period.
• Safety of Treatment With High-titer Anti- SARS-CoV-2 Plasma Versus Control as Assessed by Cumulative Incidence of Grade 3 and 4 Adverse Events [ Time Frame: Up to Day 28 ]
  Cumulative incidence of grade 3 and 4 adverse events during the study period evaluated as events per 100 person-years will be used to assess safety of the intervention.

Original Primary Outcome Measures (submitted: March 26, 2020)

Cumulative incidence of composite outcome of disease severity [ Time Frame: Day 28 ]

The cumulative incidence of composite outcome of disease severity will be used in assessing the efficacy of treatment with high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to COVID-19. This will be determined with the presence or occurrence of at least one of the following:

1. Death
2. Requiring mechanical ventilation and/or in ICU
3. non-ICU hospitalization, requiring supplemental oxygen;
4. non-ICU hospitalization, not requiring supplemental oxygen;
5. Not hospitalized, but with clinical and laboratory evidence of COVID-19 infection
6. Not hospitalized, no clinical evidence of COVID-19 infection, but with positive PCR for SARS-CoV-2

Current Secondary Outcome Measures (submitted: April 22, 2022)

Number of Participants With Severe Disease [ Time Frame: Up to 28 days ]

Number of participants with severe disease between the anti-SARS-CoV-2 convalescent plasma and control groups. Severity of disease will be measured using the number of participants with any of the disease severity categories below:

1. Death
2. Requiring mechanical ventilation and/or in ICU
3. non-ICU hospitalization, requiring supplemental oxygen
4. non-ICU hospitalization, not requiring supplemental oxygen

Original Secondary Outcome Measures (submitted: March 26, 2020)

• Anti-SARS-CoV-2 titers [ Time Frame: Baseline ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 0 (baseline).
• Anti-SARS-CoV-2 titers [ Time Frame: Day 1 ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 1.
• Anti-SARS-CoV-2 titers [ Time Frame: Day 3 ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 3.
• Anti-SARS-CoV-2 titers [ Time Frame: Day 7 ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 7.
• Anti-SARS-CoV-2 titers [ Time Frame: Day 14 ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 14.
• Anti-SARS-CoV-2 titers [ Time Frame: Day 90 ]
  Compare the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups anti-SARS-CoV-2 titers at day 90.
• Rates of SARS-CoV-2 PCR positivity [ Time Frame: Up to day 28 ]
  Compare the rates of SARS-CoV-2 PCR positivity (RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 and 28.
• Duration of SARS-CoV-2 PCR positivity [ Time Frame: Up to day 28 ]
  Compare the duration (days) of SARS-CoV-2 PCR positivity (RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 and 28.
• Peak quantity levels of SARS-CoV-2 RNA [ Time Frame: Up to day 14 ]
  Compare the peak quantity levels of SARS-CoV-2 RNA amongst the anti-SARS-CoV-2 convalescent plasma and control (SARS-CoV-2 non-immune plasma) groups at days 0, 7, 14 days.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Convalescent Plasma to Stem Coronavirus (CSSC-001)
• Official Title: Convalescent Plasma to Stem Coronavirus: A Randomized, Blinded Phase 2 Study Comparing the Efficacy and Safety Human Coronavirus Immune Plasma (HCIP) vs. Control (SARS-CoV-2 Non-immune Plasma) Among Adults Exposed to COVID-19
• Brief Summary: Evaluate the efficacy of treatment with high-titer Anti- SARS-CoV-2 plasma versus control (SARS-CoV-2 non-immune plasma) in subjects exposed to Coronavirus disease (COVID-19) at day 28.
• Detailed Description: This randomized, controlled, double-blinded phase 2 trial will assess the efficacy and safety of Anti- SARS-CoV-2 convalescent plasma as prophylaxis following exposure to COVID-19 (as defined in the inclusion criteria). Adults 18 years of age and older with high risk exposure as defined by CDC may participate. A total of 500 eligible subjects will be randomized in a 1:1 ratio to receive either high titer anti-SARS-CoV-2 plasma or control (SARS-CoV-2 non-immune plasma).
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

1:1 ratio

Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment

Condition

• Coronavirus
• Convalescence

Intervention

• Biological: Anti- SARS-CoV-2 Plasma
  SARS-CoV-2 convalescent plasma (1 unit; ~200-250 mL collected by pheresis from a volunteer who recovered from COVID-19 disease and has SARS-CoV-2 antibody titers ≥ 1:320
• Biological: SARS-CoV-2 non-immune Plasma
  Normal human plasma collected prior to December 2019

Study Arms

• Experimental: High titer anti-SARS-CoV-2 plasma
  Participants with High titer anti-SARS-CoV-2 plasma.
  Intervention: Biological: Anti- SARS-CoV-2 Plasma
• Active Comparator: SARS-CoV-2 non-immune plasma
  Participants with SARS-CoV-2 non-immune plasma.
  Intervention: Biological: SARS-CoV-2 non-immune Plasma

• Publications *: Shoham S, Bloch EM, Casadevall A, Hanley D, Lau B, Gebo K, Cachay E, Kassaye SG, Paxton JH, Gerber J, Levine AC, Currier J, Patel B, Allen ES, Anjan S, Appel L, Baksh S, Blair PW, Bowen A, Broderick P, Caputo CA, Cluzet V, Cordisco ME, Cruser D, Ehrhardt S, Forthal D, Fukuta Y, Gawad AL, Gniadek T, Hammel J, Huaman MA, Jabs DA, Jedlicka A, Karlen N, Klein S, Laeyendecker O, Lane K, McBee N, Meisenberg B, Merlo C, Mosnaim G, Park HS, Pekosz A, Petrini J, Rausch W, Shade DM, Shapiro JR, Singleton JR, Sutcliffe C, Thomas DL, Yarava A, Zand M, Zenilman JM, Tobian AAR, Sullivan D. Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection. medRxiv. 2021 Dec 14. pii: 2021.12.13.21267611. doi: 10.1101/2021.12.13.21267611. Update in: Clin Infect Dis. 2022 May 17;:.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 9, 2022): 180
• Original Estimated Enrollment (submitted: March 26, 2020): 150
• Actual Study Completion Date: June 22, 2021
• Actual Primary Completion Date: April 22, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

1. Subjects must be 18 years of age or older
2. Close contact exposure (as defined by CDC guidelines) to person with COVID-19 within 96 hours of randomization (and 120 hours of receipt of plasma)

Exclusion Criteria

1. Receipt of any blood product in past 120 days.
2. Medical, psychiatric,cognitive illness or recreational drug/alcohol use that in the opinion of the principal investigator, would affect subject safety and/or compliance.
3. Symptoms consistent with COVID-19 infection (fevers, acute onset cough, shortness of breath) at time of screening.
4. Laboratory evidence of COVID-19 infection at time of screening.
5. History or known laboratory evidence of previous COVID-19 infection.
6. History of prior reactions to transfusion blood products.
7. Inability to complete therapy with the study product within 24 hours after randomization.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04323800
• Other Study ID Numbers: IRB00245634
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Sharing is governed by Johns Hopkins University Institutional Guidelines

• Current Responsible Party: Johns Hopkins University
• Original Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Current Study Sponsor: Johns Hopkins University
• Original Study Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Not Provided

Investigators

• Principal Investigator: Shmuel Shoham, MD; Johns Hopkins University

• PRS Account: Johns Hopkins University
• Verification Date: April 2022