E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronavirus disease 2019 (COVID-19) / SARS-CoV-2 Disease |
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E.1.1.1 | Medical condition in easily understood language |
Coronavirus Disease 2019 (COVID-19) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084268 |
E.1.2 | Term | COVID-19 |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10084460 |
E.1.2 | Term | COVID-19 treatment |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084270 |
E.1.2 | Term | SARS-CoV-2 acute respiratory disease |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084272 |
E.1.2 | Term | SARS-CoV-2 infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084439 |
E.1.2 | Term | SARS-CoV-2 serology test positive |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054540 |
E.1.2 | Term | Passive immunization |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the 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 in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care.
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E.2.2 | Secondary objectives of the trial |
1. To assess overall survival, and the overall survival rate at 28, 56 and 84 days. 2. To assess SARS-CoV-2 viral clearance and load, cytokine changes over time as well as antiviral antibody titers. 3. To assess percentage of patients that required mechanical ventilation. 4. To assess time from randomization until discharge. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. PCR confirmed SARS-CoV-2 infection in a respiratory tract sample.
2. 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.
3. 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).
4. Blood hemoglobin concentration ≥ 8 g/dl.
5. Provision of written informed consent.
6. Patient is able to understand and comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations.
7. Male or female patient aged ≥ 18 years.
8. 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. |
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E.4 | Principal exclusion criteria |
1. 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.
2. Contraindication to transfusion or history of prior reactions to transfusion blood products.
3. Patients with known selective IgA deficiency.
4. Patients with mechanical ventilation and/or extracoporal membrane oxygenation (ECMO) at time of initial inclusion into the trial.
5. Participation in another trial with an investigational medicinal product.
6. Treatment with SARS-CoV-2 convalescent plasma in the past.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to clinical improvement (within 84 days) by two points on a seven point ordinal scale or live discharge from the hospital. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Treatment response is assessed daily until day 28, thereafter weekly until day 56 and finally at day 84. |
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E.5.2 | Secondary end point(s) |
- Overall survival, defined as the time from randomization until death from any cause.
- 28-day, 56-day and 84-day overall survival rates.
- SARS-CoV-2 viral clearance and load as well as antibody titers.
- Requirement mechanical ventilation at any time during hospital stay (yes/no).
- Time until discharge from randomization, taking death as competing risk into account.
- Viral load, changes in antibody titers and cytokine profiles are analyzed in an exploratory manner using paired non-parametric tests (before – after treatment). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | 0 |