NCT04456413.

Study name	Phase II randomized study of convalescent plasma from recovered COVID‐19 donors collected by plasmapheresis as treatment for subjects with early COVID‐19 infection
Methods	Trial design: randomised  Sample size: 306 Setting: outpatient, early stage, high‐risk for hospitalisation Country: USA Language: English Number of centres: 1 Trial registration number: NCT04456413 Date of registration: 2 July 2020
Participants	Inclusion criteria: Patient age > 30 years old, newly diagnosed with a COVID‐19 infection with onset of first symptoms < 96 h And least one other high‐risk feature: Age > 65 BMI ≥ 3 Hypertension, defined as SBP > 140 or DBP > 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 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 years in remission) AIDS (not just HIV‐positive) 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 scale Pneumonia by radiographic evaluation Donor eligibility criteria:  Age 18‐60 A history of a positive nasopharyngeal swab for COVID‐19 or a history of positive antibody titre 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 titres > 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 described 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) Donor exclusion criteria: NR
Interventions	Intervention(s): CP therapy Details of CP: Type of plasma: CP Volume: NR Number of doses: NR Antibody test and antibody‐titre: > 1:500 Pathogen inactivated or not: NR RT‐PCR tested: yes Details of donors:  Gender: both HLA and HNA antibody: NR Severity of disease: NR Timing from recovery from disease: at least 14 days from resolution of COVID‐19‐associated symptoms including fevers Treatment details, including time of plasma therapy (e.g. early stage of disease): hospitalised patients Comparator: nil Concomitant therapy: NR Duration of follow‐up: NR Treatment cross‐overs: nil
Outcomes	Primary study outcome: Hospitalisation rate (up to 10 days) Primary review outcomes reported All‐cause mortality: yes (60 days) Admission to hospital: yes Secondary review outcomes reported Development of severe clinical COVID‐19 symptoms, defined as WHO Clinical Progression Scale ≥ 6 (WHO 2020e): NR Time to symptom onset: NR Clinical status, assessed by need for respiratory support with standardised scales (e.g. WHO Clinical Progression Scale, WHO Ordinal Scale for Clinical Improvement) at up to 7 days, 8 to 15 days, 16 to 30 days: NR Mortality (time to event): NR 90‐day mortality: NR Length of hospital stay, for hospitalised patients: NR Admission to the intensive care unit (ICU): NR Viral clearance, assessed with RT‐PCR test: yes (day 14, 28) QoL: NR Number of participants with grade 3 and grade 4 adverse events, including potential relationship between intervention and adverse reaction (e.g. TRALI, TACO, TAD, acute transfusion reactions): NR Number of participants with serious adverse events: NR Additional outcomes:  Time to symptoms resolution Rate of nasopharyngeal swab positivity in donors Rate of donor titres level Impact of donor titres level on efficacy  Participants' anti‐SARS‐CoV2 titre assessment pre‐infusion for the treatment group, at 2 weeks, 4 weeks and 2 months Patients' cytokines levels assessment at +2 and +4 weeks post‐randomisation (time frame: 2 weeks and 4 weeks) Patients' chemokines levels assessment at +2 and +4 weeks post‐randomisation (time frame: 2 weeks and 4 weeks) Rates of adverse events (adverse effects) associated with convalescent plasma infusion (days 3, 7, 14, 28)
Starting date	November 6, 2020
Contact information	Contact: Mariefel Vendivil: 551‐996‐5828; Mariefel.Vendivil@HackensackMeridian.org Contact: Marlo Kemp: 551‐996‐4464; Marlo.Kemp@HackensackMeridian.org
Notes	Recruitment status: recruiting Prospective completion date: November 2021 Sponsor/funding: University of California, Los Angeles