A Clinical Trial to Evaluate the Efficacy of RUTI® to Reduce the Severity of SARS-CoV-2 Infection (COVID-19)

A Phase II/III, Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Efficacy of RUTI® to Reduce the Severity of SARS-CoV-2 Infection

The aim of this study is to assess the efficacy of the RUTI® vaccine in achieving clinical improvement of COVID-19 symptoms and to evaluate the safety of RUTI® in patients with SARS-CoV-2 infection. The study will include a comparison between placebo and RUTI® vaccine in a 1:1 design.

Once it has been confirmed that the patient meets the selection criteria, subjects will be randomly assigned to one of the two study groups:

• Experimental group: Administration of RUTI®
• Control group: Administration of Placebo (physiological serum)

This randomization follows a 1:1 ratio. In this way, of the total of 550 subjects who intend to be recruited for this study, 275 will receive the prophylactic treatment, and 275 will receive the placebo treatment.

Neither patient nor the doctor will know if the subject is part of the experimental group or the control group, that is to say, the treatment assignment is blind.

All subjets will receive just one inoculation of treatment (either RUTI® or Pacebo). The standard treatment of COVID-19, if is necessary, will continue after RUTI® administration according to the local guidelines.

All the subjets will be followed for one month after the first day of RUTI® or Placebo treatment.

Inclusion Criteria:

1. Sign the Informed Consent before initiating the selection procedures.
2. Patients infected with SARS-CoV-2 (PCR +) with mild symptoms up to 7 days that do not require hospitalization, from the onset of symptoms. Mild symptoms, defined as the following criteria: cough, headache, fever (>37.5ºC), muscular pain and shortness of breath.
3. People ≥ 18 years.
4. Peripheral oxygen saturation (SpO2) more than 94% on room air, not requiring supplemental oxygen.
5. Availability to meet the requirements of the protocol.

Exclusion Criteria:

1. Pregnancy or breastfeeding.

2. Suspected of active viral or bacterial infection other than SARS-CoV-2.

3. Participation in another interventional study with potentially conflicting medication within 30 days before screening.

4. Severely immunocompromised people (data gathered from preexisting medical records and history taking). This exclusion category includes:

   1. Subjects with human immunodeficiency virus (HIV-1).
   2. Neutropenic subjects with less than 500 neutrophils / mm3.
   3. Subjects with solid organ transplantation.
   4. Subjects with bone marrow transplantation.
   5. Subjects undergoing chemotherapy.
   6. Subjects with primary immunodeficiency.
   7. Severe lymphopenia with less than 400 lymphocytes / mm3.
   8. Treatment with any anti-cytokine therapy.
   9. Oral treatment with steroids, defined as daily doses of 10 mg prednisone or equivalent for more than 3 months.

5. Malignancy, or active solid or non-solid lymphoma from the previous two years.

6. BCG vaccination in the last 10 years.

7. Chloroquine or hydroxychloroquine administration in the last two weeks

8. Soy allergy

9. Direct involvement in the design or execution of the MYCOVIND clinical trial.

10. Do not have a smartphone.

11. Detection by the investigator of lack of knowledge or willingness to participate and comply with all requirements of the protocol.

12. Any other findings that, at the discretion of the investigator, may compromise compliance with the protocol or that may influence significantly the interpretation or the results of the effects of probiotics.