This is a prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2 MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects with confirmed infection by SARS-CoV-2 will receive SMT plus a total of 200-300 mL of convalescent plasma that has been pathogen-inactivated using MBT or placebo. Approximately 474 individuals will be randomized (1:1) with an interim analysis after the first 60 subjects (30 in each arm). The sample size will be re-assessed upon interim analysis. Approximately 135 individuals from selected study sites will be included in the substudy to assess the immune response and the methods of sampling. This is a prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2 MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects with confirmed infection by SARS-CoV-2 will receive SMT plus a total of 200-300 mL of convalescent plasma that has been pathogen-inactivated using MBT or placebo. Approximately 474 individuals will be randomized (1:1) with an interim analysis after the first 60 subjects (30 in each arm). The sample size will be re-assessed upon interim analysis. Approximately 135 individuals from selected study sites will be included in the substudy to assess the immune response and the methods of sampling. The investigational product will be administered by IV infusion at baseline. Participants will continue their standard medical treatment (SMT) for SARS-CoV-2 infection as prescribed by their regular physician. If applicable, SMT may be modified during the study, depending on personal requirements, the severity and progression of the disease, and need for hospitalization. Subjects' participation (from inclusion/baseline visit to the end-of-study visit) will be up to 60 days.
This is a prospective, randomized (1:1), double blind study of Convalescent anti-SARS-CoV-2
MBT Plasma (also known as convalescent plasma) plus standard medical treatment (SMT) versus
placebo plus SMT in mild or moderate COVID-19 patients who are non-hospitalised. Subjects
with confirmed infection by SARS-CoV-2 will receive SMT plus a total of 200-300 mL of
convalescent plasma that has been pathogen-inactivated using MBT or placebo.
Study candidates will voluntarily express their interest in participating in the study
through the study website or will be offered to participate at the emergency (ER) and
out-patient departments (OPD) of the participating hospitals. Candidates registered on the
website will be contacted by study physicians by phone to inform them about the study and
check their suitability for the study. Suitable candidates will be scheduled an
inclusion/baseline visit in which informed consent will be obtained (i.e., the paper informed
consent will be signed), and their eligibility will be confirmed. Candidates identified
through ER and OPD departments will undergo an inclusion/baseline visit, where the informed
consent will be obtained and eligibility will be checked. A subgroup of eligible candidates
from selected study sites will be offered participation in the substudy to assess the immune
response and the methods of sampling.
Blood and nasopharyngeal samples will be obtained from all eligible candidates. Eligible
candidates will be randomized and administered an intravenous (IV) infusion at baseline
(convalescent plasma or placebo). Both the investigator and the participant will be blinded
to the study treatment.
Specifically, subjects randomized to combination convalescent anti-SARS-CoV-2 MBT plasma plus
SMT will undergo an ABO compatibility test and will receive a single infusion of 200 to 300
ml of ABO-compatible convalescent plasma. Subjects randomized to placebo plus SMT will
receive a single infusion of 200 to 300 ml of sterile saline solution 0.9%. Infusion will be
administered at baseline, using standard procedures for administration of fresh frozen
plasma. Small adults weighing less than 45 kg will receive one infusion of 5 ml of
convalescent plasma or placebo per kilogram of body weight.
Participants will be trained on the completion of symptoms diary card and safety diary card.
The participants of the substudy will be drawn an extra tube of blood sample and will be
trained on self-collection of middle turbinate (MT) swabs and saliva, and self-collected
samples will be obtained.
The symptoms and safety diary card will be filled by the participants daily from baseline to
day 14. On follow-up visits on days 3, 7, 14, and 28, all participants will be assessed for
clinical and safety outcomes. These visits will be all by telephone except for the day 7 and
day 28 visits that will be at home and at hospital, respectively, where additionally blood
samples (only on day 7) and nasopharyngeal swabs will be collected.
At day 60 visit, all participants will be assessed by telephone for health-status outcome.
For the participants of the substudy, on day 7, an extra tube of blood sample will be
obtained and they will be asked to self-collect MT swabs and saliva. And on day 60, an extra
tube of blood sample will be obtained during an additional home or hospital visit.
Approximately 474 individuals will be randomized (1:1) with an interim analysis after the
first 60 subjects (30 in each arm).
The sample size will be re-assessed upon interim analysis. Approximately 135 individuals from
selected study sites will be included in the substudy to assess the immune response and the
methods of sampling.
The investigational product will be administered by IV infusion at baseline. Participants
will continue their standard medical treatment (SMT) for SARS-CoV-2 infection as prescribed
by their regular physician. If applicable, SMT may be modified during the study, depending on
personal requirements, the severity and progression of the disease, and need for
hospitalization.
Subjects' participation (from inclusion/baseline visit to the end-of-study visit) will be up
to 60 days.
Biological: Convalescent anti-SARS-CoV-2 MBT plasma
Subjects randomized to combination convalescent anti-SARS-CoV-2 MBT plasma plus SMT will undergo an ABO compatibility test and will receive a single infusion of 200 to 300 ml of ABO-compatible convalescent plasma
Other: Control Group
Subjects randomized to placebo plus SMT will receive one infusion of 200 to 300ml of sterile saline solution 0.9%.
Other Name: Sterile saline solution 0.9%
Inclusion Criteria:
1. 1. Adult male or female individuals of ≥50 years old.
2. 2. In women of childbearing potential1, negative pregnancy test at inclusion/baseline.
3. 3. Has confirmed SARS-CoV-2 infection as determined by PCR or validated antigen rapid
diagnostic test2 from nasopharyngeal swabs ≤5 days prior to inclusion/baseline visit.
4. 4. Symptomatic with mild or moderate COVID-19 with symptoms onset date ≤ 7 days prior
to inclusion/baseline visit.
1. a. Mild COVID-19: Individuals who have any of the common signs and/or symptoms of
COVID-19 (i.e., fever, cough, sore throat, malaise, headache, muscle pain)
without shortness of breath, dyspnoea, or abnormal chest imaging.
2. Moderate COVID-19: Individuals who have evidence of lower respiratory disease by
clinical assessment or imaging and a saturation of oxygen (SpO2) ≥94% on room air
at sea level.
5. 5. Willing to comply with the requirements of the protocol and available for follow-up
for the planned duration of the study.
6. 6. Has understood the information provided and capable of giving informed consent.
1 A woman will be considered of childbearing potential if not permanently sterilized nor
postmenopausal. Permanent sterilization methods include tubal ligation, hysterectomy and
bilateral oophorectomy. Postmenopausal is defined as 12 months with no menses without an
alternative medical cause.
2 PanbioTM COVID-19 Ag Rapid Test (Abbott), STANDARDTM Q COVID-19 Ag Test (Roche) or any
other CE marketed test for SARS-CoV-2 Ag detection.
Exclusion Criteria:
1. If female, pregnant, breastfeeding, or planning a pregnancy during the study.
2. Severe or critical COVID-19:
1. Severe COVID-19: respiratory frequency >30 breaths per minute, SpO2 <94% on room
air at sea level, ratio of arterial partial pressure of oxygen to fraction of
inspired oxygen (PaO2/FiO2) <300 mmHg, or lung infiltrates >50%.
2. Critical COVID-19: respiratory failure, septic shock, and/or multiple organ
dysfunction.
3. Current hospital admission for any cause.
4. History of previous confirmed SARS-CoV-2 infection.
5. History of significantly abnormal liver function (Child Pugh C).
6. History of chronic kidney disease (CKD) ≥ stage 4, or need of dialysis treatment.
7. Any pre-existing condition that increases risk of thrombosis.
8. History of allergic reactions to blood or plasma products or methylene blue.
9. Known IgA deficiency with anti-IgA antibodies.
10. Medical conditions for which 300ml of intravenous fluid is considered dangerous (i.e.,
decompensated heart failure or renal failure with fluid overload).
11. Inability to consent and/or comply with study requirements, in the opinion of the
investigator.
12. Currently participating or planning to participate in any interventional study for the
treatment of COVID-19 or SARS-CoV-2 infection until day 60.
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain
Hospital Sant Bernabé (Hospital de Berga)
Berga, Barcelona, Spain
CUAP Manresa (Planta 0 del CAP Bages)
Manresa, Barcelona, Spain
Hospital Universitari de Bellvitge
Barcelona, Spain