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Convalescent Plasma as Treatment for Subjects With Early COVID-19 Infection

Primary Purpose

COVID-19

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Convalescent Plasma
Best Supportive Care
Sponsored by
Hackensack Meridian Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Coronavirus, Covid19, SARS-CoV-2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Donor Eligibility Criteria:

  • Age 18-60
  • A history of a positive nasopharyngeal swab for COVID-19 or a history of positive antibody titer test.
  • At least 14 days from resolution of COVID-19-associated symptoms including fevers.
  • A negative nasopharyngeal swab (or similar test) for COVID-19
  • anti-SARS-CoV2 titers >1:500
  • Adequate venous access for apheresis
  • Meets donor eligibility criteria in accordance to Hackensack University Medical Center (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at the JTCC, and all regulatory agencies as describes in SOP 800 01.
  • Required testing of the donor and product must be performed in accordance to FDA regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30)

Recipient Eligibility Criteria:

  • Patient age >30 years old, newly diagnosed with a COVID-19 infection with onset of first symptoms < 96 hours.

  • And least one other high-risk feature:

    1. Age > 65
    2. BMI 30 or above
    3. Hypertension, defined as SBP above 140 or DBP above 90, or requiring medication for control.
    4. Coronary artery disease (history, not ECG changes only)
    5. Congestive heart failure
    6. Peripheral vascular disease (includes aortic aneurysm >= 6 cm)
    7. Cerebrovascular disease (history of CVA or TIA)
    8. Dementia
    9. Chronic pulmonary disease
    10. Liver disease (such as portal hypertension, chronic hepatitis)
    11. Diabetes (excludes diet-controlled alone)
    12. Moderate or severe renal disease defined as having a GFR < 60 mL/min
    13. Cancer (exclude if > 5 year in remission)
    14. AIDS (not just HIV positive)

Recipient exclusion criteria:

  • History of severe transfusion reaction to plasma products
  • Need for oxygen supplementation
  • Positive test for COVID-19 antibodies
  • Chemotherapy-induced neutropenia (ANC < 0.5 x 103/mcL)
  • Immunosuppressive medications except for prednisone (or steroid equivalent) > 10 mg daily.
  • Performance status < 50 by KPS
  • Pneumonia by radiographic evaluation

Sites / Locations

  • Hackensack University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Convalescent Plasma

Best Supportive Care

Arm Description

Fresh or frozen plasma will be infused one time to patients

Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.

Outcomes

Primary Outcome Measures

Hospitalization Rate
The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.

Secondary Outcome Measures

Time to Symptoms Resolution
The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.
Overall Survival Rate
Overall survival (OS) will be defined as Rate of death
Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks
Rate of Nasopharyngeal Swab Positivity in Donors
Rate of Donor Titers Level
Rate of Donor Titer Levels >1:1000
Impact of Donor Titers Level on Efficacy
Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.
Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks

Full Information

First Posted
June 30, 2020
Last Updated
September 15, 2023
Sponsor
Hackensack Meridian Health
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT04456413
Brief Title
Convalescent Plasma as Treatment for Subjects With Early COVID-19 Infection
Official Title
Phase II Randomized Study of Convalescent Plasma From Recovered COVID-19 Donors Collected by Plasmapheresis as Treatment for Subjects With Early COVID-19 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of accrual
Study Start Date
November 6, 2020 (Actual)
Primary Completion Date
April 29, 2021 (Actual)
Study Completion Date
May 4, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hackensack Meridian Health
Collaborators
United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications. Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first. Subjects will be randomized to receiving convalescent plasma or best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease. The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study.
Detailed Description
Overall study design This is a phase II randomized study of convalescent plasma for the treatment of non-immune individuals with COVID-19 infection at high risk of complications. Subjects will be considered as having completed the study after 2 months (+/- 5) days, unless consent withdrawal or death occurs first. Subjects will be randomized to receiving convalescent plasma or best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease. The final analysis will be conducted once the last subject completes the 2-month visit or withdraws from the study. A total of 306 subjects will be recruited, 153 for each arm. If a patient in the best supportive care arm requires hospitalization, the patient will be eligible to receive convalescent plasma if requested and/or deemed medically appropriate by the admitting physician. Overall study duration The study begins when the first subject (donor or recipient) signs the informed consent. The study will end once the last enrolled subject completes the study (likely a recipient). The expected duration of the study is approximately 12 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Coronavirus, Covid19, SARS-CoV-2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Convalescent Plasma
Arm Type
Experimental
Arm Description
Fresh or frozen plasma will be infused one time to patients
Arm Title
Best Supportive Care
Arm Type
Active Comparator
Arm Description
Patients will receive best supportive care. Patients randomized to best supportive care may receive plasma should they require hospitalization for progression of COVID-19 disease.
Intervention Type
Biological
Intervention Name(s)
Convalescent Plasma
Intervention Description
Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.
Primary Outcome Measure Information:
Title
Hospitalization Rate
Description
The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test.
Time Frame
10 Days
Secondary Outcome Measure Information:
Title
Time to Symptoms Resolution
Description
The time to symptoms resolution is defined as the time in days from therapies initiation to the first documented symptoms resolution as assessed by a local site. Patients whose symptoms are not resolved, or result in death, or lost follow-up on the designed follow-up date, will be censored on that date.
Time Frame
2 Months
Title
Overall Survival Rate
Description
Overall survival (OS) will be defined as Rate of death
Time Frame
2 Months
Title
Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks
Time Frame
2 Weeks
Title
Rate of Nasopharyngeal Swab Positivity in Donors
Time Frame
2 Months
Title
Rate of Donor Titers Level
Description
Rate of Donor Titer Levels >1:1000
Time Frame
2 Months
Title
Impact of Donor Titers Level on Efficacy
Time Frame
2 Months
Title
Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.
Time Frame
Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months
Title
Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks
Time Frame
4 Weeks
Other Pre-specified Outcome Measures:
Title
Plasma Product's Cytokine Level Assessment
Description
Univariate test will be performed in terms of identifying the association between exploratory objective and the hospitalization rate, Mantel-Haenszel test for categorical variables, and t-test or its non-parametric version for the continuous variables based on the normalized of the data.
Time Frame
Day 0
Title
Plasma Product's Mannose-binding Lectin (MBL) Level Assessment
Time Frame
Day 0
Title
Plasma Product's Procalcitonin (PCT) Level Assessment
Time Frame
Day 0
Title
Plasma Product's C-reactive Protein (CRP) Level Assessment
Time Frame
Day 0
Title
Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment
Time Frame
Day 0
Title
Plasma Product's Annexin V Level Assessment
Time Frame
Day 0
Title
Plasma Product's Surfactant Protein D (SP-D) Level Assessment
Time Frame
Day 0
Title
Plasma Product's microRNA Level Assessment
Time Frame
Day 0
Title
Plasma Product's Immunoglobulin Level Assessment
Time Frame
Day 0
Title
Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization
Time Frame
2 Weeks and 4 Weeks
Title
Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization
Time Frame
2 Weeks and 4 Weeks
Title
Rates of Adverse Events Associated With Convalescent Plasma Infusion.
Description
Safety assessment will be performed on infusion day for the Treatment group (immediately post infusion), and for all patients on randomization day +3 and +7 days (by telephone, closest business day is acceptable), +2 weeks (+/- 3 days), +4 weeks (+/- 3 days).
Time Frame
Day 3 and 7, Weeks 2 and 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Donor Eligibility Criteria: Age 18-60 A history of a positive nasopharyngeal swab for COVID-19 or a history of positive antibody titer test. At least 14 days from resolution of COVID-19-associated symptoms including fevers. A negative nasopharyngeal swab (or similar test) for COVID-19 anti-SARS-CoV2 titers >1:500 Adequate venous access for apheresis Meets donor eligibility criteria in accordance to Hackensack University Medical Center (HUMC) Collection Facility at the John Theurer Cancer Center (JTCC) if collecting at the JTCC, and all regulatory agencies as describes in SOP 800 01. Required testing of the donor and product must be performed in accordance to FDA regulations (21 CFR 610.40), and the donation must be found suitable (21 CFR 630.30) Recipient Eligibility Criteria: Patient age >30 years old, newly diagnosed with a COVID-19 infection with onset of first symptoms < 96 hours. And least one other high-risk feature: Age > 65 BMI 30 or above Hypertension, defined as SBP above 140 or DBP above 90, or requiring medication for control. Coronary artery disease (history, not ECG changes only) Congestive heart failure Peripheral vascular disease (includes aortic aneurysm >= 6 cm) Cerebrovascular disease (history of CVA or TIA) Dementia Chronic pulmonary disease Liver disease (such as portal hypertension, chronic hepatitis) Diabetes (excludes diet-controlled alone) Moderate or severe renal disease defined as having a GFR < 60 mL/min Cancer (exclude if > 5 year in remission) AIDS (not just HIV positive) Recipient exclusion criteria: History of severe transfusion reaction to plasma products Need for oxygen supplementation Positive test for COVID-19 antibodies Chemotherapy-induced neutropenia (ANC < 0.5 x 103/mcL) Immunosuppressive medications except for prednisone (or steroid equivalent) > 10 mg daily. Performance status < 50 by KPS Pneumonia by radiographic evaluation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele L Donato, MD
Organizational Affiliation
Hackensack Meridian Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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Convalescent Plasma as Treatment for Subjects With Early COVID-19 Infection

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