Trial With or Without Infusion of SARS-CoV-2 Antibody Containing Plasma in High-Risk Patients With COVID-19

Study Overview
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Brief Summary
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The study RECOVER is a randomized, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent/vaccine-boosted plasma or standard of care.

Detailed Description
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The aim of this randomized phase-II study is to gain evidence on the effect of convalescent plasma/vaccine-boosted plasma in the treatment of SARS-CoV-2 infection in high-risk patients. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorized in 4 groups: group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. group 2, chronic immunosuppression not meeting the criteria of group 1 group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2 The duration of the trial for each patient is expected to be about 3 months, including two days of intervention (infusion of CP/PVP), followed by a follow-up of 3 months. Furthermore viral load is measured in nasopharagyngeal swabs at day 1, 3, 5, 10, 14, 28 or until hospital discharge within 84 days after randomization. Treatment response is assessed daily until day 28, thereafter weekly until day 56, and finally at day 84. Patients randomized into the standard arm of the study have the possibility to cross over into the experimental arm of the study starting at day 10 (+ 2 days) in case of not improving or worsening clinical condition. In total 174 patients are planned to be enrolled in the study.

Official Title
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A Randomized Open Label Phase-II Clinical Trial With or Without Infusion of Plasma From Subjects After Convalescence of SARS-CoV-2 Infection in High-Risk Patients With Confirmed Severe SARS-CoV-2 Disease

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Other: Convalescent/Vaccine-boosted Plasma (CP/PVP)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PCR confirmed SARS-CoV-2 infection in a respiratory tract sample. Oxygen saturation (SaO2) of 94% or less while breathing ambient air or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 300 mm Hg. High risk due to either pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less (group 1) and/or chronic immunosuppression not meeting the criteria of group 1 (group 2) and/or Age ≥ 50 -75 years meeting neither the criteria of group 1 nor group 2 (group 3) and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL and/or Age ≥ 75 years meeting neither the criteria of group 1 nor group 2 (group 4). Blood hemoglobin concentration ≥ 8 g/dl. Provision of written informed consent. Patient is able to understand and comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations. Male or female patient aged ≥ 18 years Postmenopausal or evidence of non-childbearing status. For women of childbearing potential: negative urine or serum pregnancy test within 14 days prior to study treatment. Exclusion Criteria: Dementia, psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the principle investigator, would affect subject safety and/or compliance. Contraindication to transfusion or history of prior reactions to transfusion blood products. Patients with selective IgA deficiency. Patients with mechanical ventilation and/or extracoporal membrane oxygenation (ECMO) at time of initial inclusion into the trial. Mechanical ventilation is defined as either NIV - non-invasive ventilation or positive pressure ventilation. Enrollment into another clinical trial evaluating specific therapies for COVID-19 is encouraged. Participation in another trial with an investigational medicinal product. Treatment with SARS-CoV-2 convalescent/vaccine-boosted plasma in the past.

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/Vaccine-boosted Plasma<br>Infusion of plasma on day 1 and 2 (238 - 337 ml anti-SARS-Cov-2 CP/PVP each) | Other: Convalescent/Vaccine-boosted Plasma (CP/PVP)<br>* Plasma from apheresis obtained from donors, who have recovered from SARS-CoV-2 infection or received a successful vaccination against SARS-CoV-2. CP/PVP infusion is administered on two following days. Each CP/PVP bag contains approx. 238 - 337 ml anti-SARS-Cov-2 CP/PVP for infusion.<br>|
| No Intervention: Standard of Care<br>No intervention - standard therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Improvement | Time from randomization until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital | within 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate | Overall survival and overall survival rate at 28, 56 and 84 days | within 84 days | 
| Viral clearance | SARS-CoV-2 viral clearance and load | within 84 days | 
| Cytokine profiles | Cytokine changes over time | within 84 days | 
| Antibody titres | Measurement of antiviral antibody titres | within 84 days | 
| Requirement of mechanical ventilation | Percentage of patients that required mechanical ventilation | within 84 days | 
| Discharge from hospital | Time from randomization until discharge | within 84 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High risk patients, convalescent plasma, post vaccination plasma, COVID-19