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

• ClinicalTrials.gov Identifier: NCT04323800
• Recruitment Status: Recruiting
• First Posted: March 27, 2020
• Last Update Posted: November 9, 2020
• 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
• Last Update Posted Date: November 9, 2020
• Actual Study Start Date: June 10, 2020
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 15, 2020)

• Efficacy of treatment at Day 28 [ 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 - 1 [ Time Frame: Up to Day 28 ]
  Cumulative incidence of serious adverse events categorized separately as either severe infusion reactions and Acute Respiratory Distress Syndrome during the study period.
• Safety of treatment with high-titer Anti- SARS-CoV-2 plasma versus control - 2 [ Time Frame: Up to Day 28 ]
  Cumulative incidence of grade 3 and 4 adverse events during the study period

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: July 15, 2020)

Cumulative incidence of disease severity [ Time Frame: up to Day 28 ]

Cumulative incidence of disease severity between the anti-SARS-CoV-2 convalescent plasma and control groups after individuals develop SARS-CoV-2 infection. Severity of disease will be measured using a clinical event scale of disease severity (evaluated up to Day 28):

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

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 (submitted: July 15, 2020)

• Anti-SARS-CoV-2 titers Day 0 [ Time Frame: Day 0 ]
  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 or day 0 (baseline).
• Anti-SARS-CoV-2 titers Day 1 [ 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 Day 7 [ 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 Day 14 [ 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 Day 90 [ 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 28 ]
  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, 1, 7, 14 and 28 days.

• 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 *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 15, 2020): 500
• Original Estimated Enrollment (submitted: March 26, 2020): 150
• Estimated Study Completion Date: January 2023
• Estimated Primary Completion Date: December 31, 2022 (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: Shmuel Shoham, MD; 410-614-6702; TOID_CRC@jhmi.edu

• 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

• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University
• Collaborators: Not Provided

Investigators

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

• PRS Account: Johns Hopkins University
• Verification Date: October 2020