E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COVID-19 or protective effect against in B-cell depleted patients or vaccination non-responders |
COVID-19 of bescherming tegen deze infectie bij B-cel gedepleteerde patiënten of non-responders op vaccinatie. |
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E.1.1.1 | Medical condition in easily understood language |
Patient with a weakened immune system |
Patiënten met een verminderd immuunsysteem |
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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 | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084464 |
E.1.2 | Term | COVID-19 immunization |
E.1.2 | System Organ Class | 100000004865 |
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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 create a population pharmacokinetic model of SARS-COV-2 neutralizing antibodies as present in ConvP and Nanogam plus. |
Het ontwikkelen van een farmacokinetisch model van SARS-CoV2- neutraliserende antilichamen, aanwezig in ConvP en Nanogam plus. |
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E.2.2 | Secondary objectives of the trial |
We will test this on patients with B-cell depletion and/or dysfunction or patients who are non-responder on vaccination. Because they are unable or hardly able to make neutralizing antibodies themselves, this could give them a protective effect against COVID19.
Safety of convalescent plasma or nanogam will be evaluated |
Dit zal getest worden op patiënten met B-cel depletie of dysfunctie of op patiënten die geen antistoffen aanmaken na vaccinatie. Deze groep heeft echter weinig tot geen kans tot aanmaken van eigen neutraliserende antistoffen. Dit zou hen een protectief effect kunnen geven tegen een COVID-19 infectie.
Veiligheid van convalescent plasma of nanogam zullen geëvalueerd |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
18 years or older Written informed consent ● B-cell depleted status because one of following: o Prior B-cell depletion therapy (latest administration < 6 months prior to inclusion) o Immunodeficiency requiring IVIG suppletion ● Wantai total Ig antibody optical density (OD) ratio of 2.0 or lower 2 weeks after complete vaccination against COVID-19 |
18 jaar of ouder, Geïnformeerde toestemming gegeven ● B-cel gedepleteerde status na één van volgende: o B-cel depleterende therapie (laatste toediening <6 maanden voor inclusie) o Immuundeficiëntie waarvoor toediening van IVIG noodzakelijk is ● Wantai total Ig antibody optical density (OD) ratio =2.0 of lager 2 weken na volledige vaccinatie tegen COVID-19 |
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E.4 | Principal exclusion criteria |
Symptoms of respiratory infection at time of inclusion Anti-SARS-CoV-2 antibodies prior to administration of study product > 2.0 OD (Wantai total Ig) Positive SARS-CoV-2 PCR Known previous history of transfusion-related acute lung injury Known IgA deficiency Known hypersensitivity to human immunoglobulins Liver cirrhosis Received anti-SARS-CoV-2 vaccination in the 2 weeks preceding screening or between screening and baseline |
Symptomen van een bovenste luchtweginfectie Anti-SARS-CoV2 antilichamen voor toediening van het studieproduct > 2.0 OD (Wantai total Ig) Positieve SARS-CoV-2 PCR Voorgeschiedenis van transfusie-gerelateerde acute longschade Gekende IgA deficiëntie Gekende overgevoeligheid aan humane immunoglobulines Levercirrose Anti-SARS-CoV-2 vaccinatie 2 weken of minder voor screening of tussen screening en inclusie |
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E.5 End points |
E.5.1 | Primary end point(s) |
Main study parameter/endpoint • Duration and titers of virus neutralizing antibodies in serum of patients after the administration of different doses of ConvP
• Duration and titers of virus neutralizing antibodies in serum of patients after the administration of different doses of Nanogamplus
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Primair eindpunt: - Duur en titer van virus neutraliserende antilichamen in patiëntenserum na toediening van convalescent plasma.
- Duur en titer van virus neutraliserende antilichamen in patiëntenserum na toediening van Nanogam plus.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Control of titer before administration of study product. One and 24 hours post-administration. on day 3 and 7 After 2, 4, 6, 8, 12, 18 and 24 weeks |
Controle van antistoftiter: Voor toediening van studieproduct Na 1 en 24 uur Op dag 3 en 7 Na 2, 4, 6, 8, 12, 18 en 24 weken
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E.5.2 | Secondary end point(s) |
• The incidence of COVID-19 during follow-up until antibody levels have become undetectable • Percentage of patients with adverse events (in particular TRALI of TACO) after administration of convalescent plasma • Percentage of patients with adverse events (in particular TRALI or TACO) after administration of Nanogamplus Other study parameters (if applicable) • Whenever a breakthrough infection is diagnosed, we will do everything possible to collect the SARS-CoV-2 strain for sequencing in order to identify new or emerging variants of concern (e.g. strain 501.V2 or P.1 also known as the South-African or Brazilian variant) to evaluate the virus neutralizing capacity of the ConvP or Nanogamplus that the patient received.
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- Incidentie van COVID-19 tijdens follow-up van antilichaam titers tot ze niet meer detecteerbaar zijn.
- Percentage van patiënten met ernstige bijwerkingen (TRALI, TACO) na toediening van convalescent plasma - Percentage van patiënten met ernstige bijwerkingen (TRALI, TACO) na toediening van Nanogam plus
Indien er een doorbraakinfectie gediagnosticeerd is, zal er geprobeerd worden het virus-strain te isoleren en sequencen ter opsporing van mutanten (zoals de Zuid-Afrikaanse of Britse variant) om zo de virus neutraliserende capaciteit van het toegediende middel te evalueren. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Control of titer before administration of study product. One and 24 hours post-administration. After 3 and 7 days After 2, 4, 6, 8, 12, 18 and 24 weeks |
Controle van antistoftiter: Voor toediening van studieproduct Na 1 en 24 uur Na 3 en 7 dagen Na 2, 4, 6, 8, 12, 18 en 24 weken
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Determining the perfect dose of convalescent plasma or Nanogam. |
Determinering van de perfecte dosis convalescent plasma of Nanogam |
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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 | No |
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 | No |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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Last visit last subject
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Laatste bezoek van laatste patiënt |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |