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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Randomized Study of Convalescent Plasma From Recovered COVID-19 Donors Collected by Plasmapheresis as Treatment for Subjects With Early COVID-19 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Convalescent Plasma
* Other: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma<br>Fresh or frozen plasma will be infused one time to patients | Biological: Convalescent Plasma<br>* Fresh or frozen plasma will be infused one time to hospitalized patients with COVID-19 infection<br>|
| Active Comparator: Best Supportive Care<br>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. | Other: Best Supportive Care<br>* Patients will receive best supportive care. Patients randomized to this arm may receive plasma should they require hospitalization for progression of COVID-19 disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospitalization Rate | The hospitalization rate will be summarized by frequency (%) and compared between the Treatment and Control arms by Mantel-Haenszel test. | 10 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 Months | 
| Overall Survival Rate | Overall survival (OS) will be defined as Rate of death | 2 Months | 
| Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks |  | 2 Weeks | 
| Rate of Nasopharyngeal Swab Positivity in Donors |  | 2 Months | 
| Rate of Donor Titers Level | Rate of Donor Titer Levels >1:1000 | 2 Months | 
| Impact of Donor Titers Level on Efficacy |  | 2 Months | 
| Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months. |  | Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months | 
| Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks |  | 4 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus, Covid19, SARS-CoV-2