Clinical trial NCT04456413: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus
Covid19
SARS-CoV-2
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2020-07-02
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Hospitalization Rate
timeFrame: 10 Days
Secondary outcomes:
measure: Time to Symptoms Resolution
timeFrame: 2 Months
measure: Overall Survival Rate
timeFrame: 2 Months
measure: Rate of Virologic Clearance by Nasopharyngeal Swab at 2 Weeks
timeFrame: 2 Weeks
measure: Rate of Nasopharyngeal Swab Positivity in Donors
timeFrame: 2 Months
measure: Rate of Donor Titers Level
timeFrame: 2 Months
measure: Impact of Donor Titers Level on Efficacy
timeFrame: 2 Months
measure: Patients' Anti-SARS-CoV2 Titer Assessment Pre-infusion for the Treatment Group, at 2 Weeks , 4 Weeks and 2 Months.
timeFrame: Prior to treatment, 2 Weeks, 4 Weeks, and 2 Months
measure: Rate of Virologic Clearance by Nasopharyngeal Swab at 4 Weeks
timeFrame: 4 Weeks
Other outcomes:
measure: Plasma Product's Cytokine Level Assessment
timeFrame: Day 0
measure: Plasma Product's Mannose-binding Lectin (MBL) Level Assessment
timeFrame: Day 0
measure: Plasma Product's Procalcitonin (PCT) Level Assessment
timeFrame: Day 0
measure: Plasma Product's C-reactive Protein (CRP) Level Assessment
timeFrame: Day 0
measure: Plasma Product's Human Neutrophil Lipocalin (HNL) Level Assessment
timeFrame: Day 0
measure: Plasma Product's Annexin V Level Assessment
timeFrame: Day 0
measure: Plasma Product's Surfactant Protein D (SP-D) Level Assessment
timeFrame: Day 0
measure: Plasma Product's microRNA Level Assessment
timeFrame: Day 0
measure: Plasma Product's Immunoglobulin Level Assessment
timeFrame: Day 0
measure: Patients' Cytokines Levels Assessment at +2 and +4 Weeks Post Randomization
timeFrame: 2 Weeks and 4 Weeks
measure: Patients' Chemokines Levels Assessment at +2 and +4 Weeks Post Randomization
timeFrame: 2 Weeks and 4 Weeks
measure: Rates of Adverse Events Associated With Convalescent Plasma Infusion.
timeFrame: Day 3 and 7, Weeks 2 and 4
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Hackensack Meridian Health
name: Michele L Donato, MD
role: PRINCIPAL_INVESTIGATOR
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