Clinical Trial to Evaluate the Efficacy of RUTI® Against SARS-COV-2 Infection (COVID-19) in Healthcare Workers

• ClinicalTrials.gov Identifier: NCT04453488
• Recruitment Status: Not yet recruiting
• First Posted: July 1, 2020
• Last Update Posted: July 29, 2020
• Sponsor: Fundació Institut Germans Trias i Pujol
• Information provided by (Responsible Party): Fundació Institut Germans Trias i Pujol

Tracking Information

• First Submitted Date: June 30, 2020
• First Posted Date: July 1, 2020
• Last Update Posted Date: July 29, 2020
• Estimated Study Start Date: July 30, 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2020)

Documented cumulative incidence of SARS-CoV-2 infection [ Time Frame: Up to 4 months ]

% positive serology at the end of the study or positive PCR test in the course of routine clinical practice

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 27, 2020)

• Sick leave for SARS-CoV-2 [ Time Frame: Up to 4 months ]
  Number of days of documented sick leave for SARS-CoV-2
• Days off work due to the quarantine [ Time Frame: Up to 4 months ]
  The number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2
• Quarantine imposed by close contact outside the center with SARS-CoV-2 positive [ Time Frame: Up to 4 months ]
  Number of days of quarantine imposed by close contact outside the center with SARS-CoV-2 positive
• Professional category [ Time Frame: Up to 4 months ]
  Number of MD, nursing, personnel management and services, etc.
• Fever [ Time Frame: Up to 4 months ]
  Number of days of self-reported fever (≥38 ºC)
• Incidence of self-reported acute respiratory symptoms [ Time Frame: Up to 4 months ]
  Cumulative incidence of self-reported acute respiratory symptoms
• Days of self-reported acute respiratory symptoms [ Time Frame: Up to 4 months ]
  Number of days of self-reported acute respiratory symptoms
• Incidence of pneumonia [ Time Frame: Up to 4 months ]
  Number of participants with pneumonia confirmed by X-ray
• Incidence of death from SARS-CoV-2 infection [ Time Frame: Up to 4 months ]
  Cumulative incidence of death from documented SARS-CoV-2 infection
• Incidence of admissions to Intensive Care Unit (ICU) [ Time Frame: Up to 4 months ]
  Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection
• Days in ICU [ Time Frame: Up to 4 months ]
  Number of days admitted to the ICU for documented SARS-CoV-2 infection
• Incidence of mechanical ventilation [ Time Frame: Up to 4 months ]
  Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection
• Incidence of hospital admissions [ Time Frame: Up to 4 months ]
  Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection
• Days of hospitalization [ Time Frame: Up to 4 months ]
  Number of days of hospitalization for documented SARS-CoV-2 infection
• Incidence of SARS-CoV-2 antibodies [ Time Frame: Final visit ]
  Incidence of SARS-CoV-2 antibodies at the end of the study period
• Types of antibodies detected [ Time Frame: Final visit ]
  Frequency and levels of immunoglobulin IgG and immunoglobulin IgM
• Levels of SARS-CoV-2 antibodies [ Time Frame: Final visit ]
  Levels of SARS-CoV-2 antibodies at the end of the study period

Original Secondary Outcome Measures (submitted: June 30, 2020)

• Sick leave for SARS-CoV-2 [ Time Frame: Up to 4 months ]
  Number of days of documented sick leave for SARS-CoV-2
• Days off work due to the quarantine [ Time Frame: Up to 4 months ]
  The number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2
• Quarantine imposed by close contact outside the center with SARS-CoV-2 positive [ Time Frame: Up to 4 months ]
  Number of days of quarantine imposed by close contact outside the center with SARS-CoV-2 positive
• Professional category [ Time Frame: Up to 4 months ]
  Number of MD, nursing, personnel management and services, etc.
• Fever [ Time Frame: Up to 4 months ]
  Number of days of self-reported fever (≥38 ºC)
• Incidence of self-reported acute respiratory symptoms [ Time Frame: Up to 4 months ]
  Cumulative incidence of self-reported acute respiratory symptoms
• Days of self-reported acute respiratory symptoms [ Time Frame: Up to 4 months ]
  Number of days of self-reported acute respiratory symptoms
• Incidence of pneumonia [ Time Frame: Up to 4 months ]
  Number of participants with pneumonia confirmed by X-ray
• Incidence of death from SARS-CoV-2 infection [ Time Frame: Up to 4 months ]
  Cumulative incidence of death from documented SARS-CoV-2 infection
• Incidence of admissions to ICU [ Time Frame: Up to 4 months ]
  Cumulative incidence of admissions to intensive care for documented SARS-CoV-2 infection
• Days in ICU [ Time Frame: Up to 4 months ]
  Number of days admitted to the ICU for documented SARS-CoV-2 infection
• Incidence of mechanical ventilation [ Time Frame: Up to 4 months ]
  Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection
• Incidence of hospital admissions [ Time Frame: Up to 4 months ]
  Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection
• Days of hospitalization [ Time Frame: Up to 4 months ]
  Number of days of hospitalization for documented SARS-CoV-2 infection
• Incidence of SARS-CoV-2 antibodies [ Time Frame: Final visit ]
  Incidence of SARS-CoV-2 antibodies at the end of the study period
• Types of antibodies detected [ Time Frame: Final visit ]
  Frequency and levels of IgG and IgM
• Levels of SARS-CoV-2 antibodies [ Time Frame: Final visit ]
  Levels of SARS-CoV-2 antibodies at the end of the study period

Current Other Pre-specified Outcome Measures (submitted: June 30, 2020)

• AEs [ Time Frame: Up to 4 months ]
  All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection as part of the associated symptoms.
• SAEs [ Time Frame: Up to 4 months ]
  All those Adverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Clinical Trial to Evaluate the Efficacy of RUTI® Against SARS-COV-2 Infection (COVID-19) in Healthcare Workers
• Official Title: Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Efficacy of the RUTI® Vaccine to Prevent SARS-CoV-2 Infection
• Brief Summary: The purpose of this study is to assess the efficacy of RUTI® vaccine preventing SARS-CoV-2 infection (COVID-19) in healthcare workers.
• Detailed Description: The aim of this study is to assess the efficacy of RUTI® vaccine preventing SARS-CoV-2 infection (COVID-19) in healthcare workers. The study will include a comparison between placebo and RUTI® vaccine.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention

Condition

• Covid-19
• Sars-CoV2

Intervention

• Biological: RUTI® vaccine
  Each dose of the RUTI® vaccine contains 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli.
• Biological: Placebo
  Physiological serum, 0.9% NaCl, will be used as a placebo

Study Arms

• Experimental: RUTI® vaccine
  Participants will receive two dose of RUTI® vaccine at the baseline visit and after 2 weeks +/- 3 days, which will be administered subcutaneously in the deltoid region at a dose of 25 µg of fragmented, purified and liposomed heat-inactivated Mycobacterium tuberculosis bacilli in an injection volume of 0.3 mL.
  Intervention: Biological: RUTI® vaccine
• Placebo Comparator: Placebo
  Participants will receive two dose of physiological serum will be administered subcutaneously in the deltoid region at the baseline visit and after 2 weeks +/- 3 days.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: June 30, 2020): 315
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Sign the Informed Consent before initiating the selection procedures.
2. Healthcare system workers working in contact with subjects potentially infected with SARS-CoV-2.
3. People ≥ 18 years.
4. Willingness to meet the requirements of the protocol.
5. Negative Rapid Serological Test of SARS-CoV-2
6. The participant must agree to use effective contraceptive methods during the study period, in case of childbearing age.

Exclusion Criteria:

1. Previous SARS-CoV-2 infection
2. Pregnancy. Pregnancy test will be performed in case of doubt.
3. Breastfeeding.
4. Suspected of active viral or bacterial infection.
5. Symptoms compatible with COVID-19, despite a negative polymerase chain reaction (PCR) test.
6. Vaccination in the last 4 weeks or planned vaccination during the study period, except for influenza vaccine.
7. Participation in a research that requires experimental intervention (does not include observational studies) in the previous month before signing the Consent or during the study.

8. Severely immunocompromised people. 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.
9. Malignancy, or active solid or non-solid lymphoma from the previous two years.
10. BCG vaccination in the last 1year.
11. Soy allergy.

12 Chloroquine or hydroxychloroquine administration in the last two weeks.

13. Direct involvement in the design or execution of the RUTICOVID19 clinical trial.

14 Retirement, transfer, long-term leave (> 1 month) due to scheduled surgery or any other event that makes it impossible to work in person at your health center during the months following the recruitment to the study.

15. Employee at the health center <22 hours per week.

16. Do not have a smartphone.

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

18. Any other findings that, at the discretion of the researcher, may compromise compliance with the protocol or that may influence significantly the interpretation or the results of the effects of the vaccine.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Pere-Joan Cardona, MD, PhD; +34 93 033 0527 ext 6400; pjcardona@igtp.cat

• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04453488
• Other Study ID Numbers: RUTICOVID19
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Fundació Institut Germans Trias i Pujol
• Study Sponsor: Fundació Institut Germans Trias i Pujol
• Collaborators: Not Provided

Investigators

• Study Chair: Pere-Joan Cardona, MD, PhD; IGTP

• PRS Account: Fundació Institut Germans Trias i Pujol
• Verification Date: July 2020