COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-006621-22/DE

IKT Ulm - Sixten Körper

s.koerper@blutspende.de

2021-12-23

Completed

RCT

Randomized

Parallel

Open label

multi-center

Treatment

Two patient populations will be included in the study: (1) unvaccinated elderly and high COVID-age population and (2) high-risk immunocompromised population. (1) Unvaccinated elderly and high COVID-age population: 1. SARS-CoV-2 RNA or SARS-CoV-2 antigen detected in a specimen, ≤ 7 days after onset of symptoms 2. Symptoms of COVID-19 (so including but not limited to: fever, cough, breathlessness, chest pain, wheeze, sore throat, haemoptysis, runny nose, fatigue, muscle or joint pain, confusion, headache, seizures, nausea, vomiting, diarrhoea, abdominal pain, poor appetite, skin ulcers or rash, ear pain, conjunctivitis, anosmia, bleeding, lymphadenopathy.52 The attending clinician will determine if symptoms are consistent with COVID-19. 3. Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support 4. Ability to transfuse (per randomisation) within 7 days after onset of symptoms 5. Men or women, 70 years or older OR under 70 years with significant comorbidities (arterial hypertension, diabetes, obesity, asthma or other chronic pulmonary disease, cardiovascular disease, cerebrovascular disease, chronic kidney disease / dialysis, liver disease, chronic neurological disease, rheumatoid arthritis, lupus or psoriasis) resulting in a ‘COVID-age’ of 70 years or more according to the ALAMA risk calculator https://alama.org.uk/covid-19-medical-risk-assessment/ 6. Signed written informed consent (2) High-risk immunocompromised population 1. SARS-CoV-2 RNA or SARS-CoV-2 antigen detected in a specimen, ≤ 7 days after onset of symptoms 2. Symptoms of COVID-19 (so including but not limited to: fever, cough, breathlessness, chest pain, wheeze, sore throat, haemoptysis, runny nose, fatigue, muscle or joint pain, confusion, headache, seizures, nausea, vomiting, diarrhoea, abdominal pain, poor appetite, skin ulcers or rash, ear pain, conjunctivitis, anosmia, bleeding, lymphadenopathy.52 The attending clinician will determine if symptoms are consistent with COVID-19. 3. Clinical status not requiring admission to hospital for COVID-19 disease and oxygen support 4. Ability to transfuse (per randomisation) within 7 days after onset of symptoms 5. Male or female Adult ≥18 years of age with extremely high risk including: a. Patients with at least one of the following acquired immune deficiencies: i. Lymphoid malignancies treated within the last 12 months ii. Lymphoid malignancies with persistent hypogammaglobulinaemia (IgG < 5 g/L) iii. Myeloid malignancies treated by chemotherapy within the last 12 months iv. Myeloid malignancies treated with anti-BCL-2 drugs within the last 12 months v. Myeloid malignancies associated with prolonged neutropenia (≥ 6 weeks) vi. Solid tumour undergoing treatment with chemotherapy (until 3 months after completion of the last chemotherapy cycle). vii. Allogenic hematopoietic stem cell transplantation within the last 12 months or anytime if on-going treatment for chronic GVHD viii. Organ transplantation ix. Anti - B (CD20/CD19) MoAb and/or mycophenolate mofetil treatment within the last 12 months x. Anti-CD19/CD20 CAR-T cell treatment xi. ATG or alemtuzumab treatment within the last 6 months xii. AIDS or b. Patients with primary lymphoid immune deficiencies: i. B cell deficiencies (such as Bruton agammaglobulinemia) ii. T cell deficiencies (such as Wiskott Aldrich disease) iii. Combined deficiencies (such as Common variable immunodeficiency ) or c. Patients without detectable seroconversion ≥ 3 weeks after complete vaccination schedule with an approved vaccine. 6. Signed written informed consent

(1) Unvaccinated elderly and high COVID-age population: 1. Age < 18 years 2. Prior or concurrent treatment for COVID-19 (unless listed as authorized specific treatment in the Appendix) 3. History of documented SARS-CoV-2 infection in the last 90 days prior to enrolment 4. Prior anti-SARS-CoV-2 immunization 5. Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components 6. Known participant objection to receiving plasma products 7. Primary or acquired immune deficiency listed below (see cohort 2) 8. Refusal to participate expressed by patient or legally authorised representative 9. Pregnancy (2) High-risk immunocompromised population 1. Age < 18 years 2. Prior or concurrent treatment for COVID-19 (dexamethasone, anti-IL-6/IL6R, remdesivir) except for prophylactic administration of anti-SARS-Cov2 monoclonal antibodies (pre or post exposure) in cohort 2 and authorized specific treatment in the Appendix) 3. History of documented SARS-CoV-2 infection in the last 90 days prior to enrollment 4. Contraindication to receiving CCP including previous history of transfusion-related acute lung injury (TRALI) or moderate or severe allergic reaction to blood components 5. Known participant objection to receiving plasma products 6. Refusal to participate expressed by patient or legally authorised representative 7. Pregnancy Any patient eligible for both cohorts will be included in cohort 2. Enrolment in other trials after reaching the primary end-point is authorised.

2

DRK-Blutspendedienst Baden-Württemberg - Hessen gGmbH

18

100

France;Netherlands;Germany;United Kingdom

Mild disease at enrollment

1: Mild disease at enrollment

226

Primary endpoint definition: the proportion of patients hospitalised or death by day 28. The primary outcome will be analysed using logistic regression adjusted for randomisation stratification variables (results will be expressed as odds ratios with 95% confidence intervals). Adjustment for major prognostic factors will be considered depending on the evolution of medical knowledge on the prognosis of patients infected by SARS-Cov-2.

Declared number of arm (2.0) differs from found arms (1.0)

Phase 3

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