E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
The intervention has a protective objective which is to improve the clinical course of coronavirus infection in Health Care Workers. Health Care Workers are, in general, healthy. |
|
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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10047490 |
E.1.2 | Term | Virus identification and serology |
E.1.2 | System Organ Class | 100000004848 |
|
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 |
1. To determine if BCG vaccination (Intervention) compared with placebo (Comparator) reduces the incidence of COVID-19 disease (Outcome) measured over the 6 months following randomisation (Time) in healthcare workers exposed to SARS-CoV-2 (Participants). 2. To determine if BCG vaccination (Intervention) compared with placebo (Comparator) reduces the incidence of severe COVID-19 disease (with COVID 19 related death, hospitalisation, or non-hospitalised severe disease (defined as Non-ambulant1 for ≥ 3 consecutive days OR Unable to work2 for ≥ 3 consecutive days) (Outcome) measured over the 6 months following randomisation (Time) in healthcare workers exposed to SARS-CoV-2 (Participants).
|
|
E.2.2 | Secondary objectives of the trial |
3. To determine if BCG vaccination compared with placebo reduces the incidence of COVID-19 disease measured over the 12 months 4. To determine if BCG vaccination compared with placebo reduces the incidence of severe COVID-19 disease measured over the 12 months 5. To determine if BCG vaccination compared with placebo prolongs the time to first SARS-CoV-2-proven respiratory illness measured over 6 and 12 months 6. To determine if BCG vaccination compared with placebo reduces the severity of COVID-19 disease measured over 6 and 12 months 7. To determine if BCG vaccination compared with placebo reduces the rate and severity of illness measured over 6 and 12 months
8. To determine if BCG vaccination compared with placebo reduces absenteeism in healthcare workers
9. To evaluate the safety of BCG vaccination in adult healthcare workers.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Over 18 years of age • Healthcare worker • Provide a signed and dated informed consent form • Pre-randomisation blood collected
|
|
E.4 | Principal exclusion criteria |
1 Has any BCG vaccine contraindication o Fever or generalised skin infection (where feasible, randomisation can be delayed until cleared) o Weakened resistance toward infections due to a disease in/of the immune system o People with any serious underlying illness (such as malignancy) o Known or suspected HIV infection,11 even if they are asymptomatic or have normal immune function. o People with active skin disease such as eczema, dermatitis or psoriasis at or near the site of vaccination o Pregnant o Another live vaccine administered in the month prior to randomisation o Require another live vaccine to be administered within the month following BCG randomisation o Known anaphylactic reaction to any of the ingredient present in the BCG vaccine o Previous active TB disease o Currently receiving long term (more than 1 month) treatment with isoniazid, rifampicin or quinolone as these antibiotics have activity against Mycobacterium bovis 2 Previous adverse reaction to BCG vaccine (significant local reaction (abscess) or suppurative lymphadenitis) 3 BCG vaccine given within the last year 4 Have previously had a SARS-CoV-2 positive test result (positive PCR on a respiratory sample or a positive SARS-CoV-2 diagnostic antigen test approved by the local jurisdiction’s public health policy 5 Already part of this trial, recruited at a different hospital. 6 Participation in another COVID-19 prevention trial 7 Have previously received a COVID-19 specific vaccine |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of participants with COVID-19 disease Number or participants with severe of COVID-19 disease |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Number of participants with COVID-19 disease Number or participants with severe of COVID-19 disease Time to first symptom of COVID-19 in a participant Number of episodes of COVID-19 disease Number of participants with asymptomatic SARS-CoV-2 infection Number of days unable to work due to COVID-19 disease Number of days confined to bed due to COVID-19 disease Number of days with symptoms in any episode of illness for COVID-19 disease Number of pneumonia cases (abnormal chest X-ray) associated with a positive SARS-CoV-2 test Need for oxygen therapy associated with a positive SARS-CoV-2 test Number of admission to critical care and duration of stay associated with a positive SARS-CoV-2 test Need of mechanical ventilation and duration and a positive SARS-CoV-2 test Duration of hospitalisation due to COVID-19 Number of deaths associated with a positive SARS-CoV-2 test Number of participants with fever or respiratory illnessNumber of episodes of fever or respiratory illness Number of days unable to work due to fever or respiratory illness Number of days confined to bed due to fever or respiratory illness Number of days with symptoms in any episode of illness Number of pneumonia cases (abnormal chest X-ray) Need for oxygen therapy Number of admission to critical care Need of mechanical ventilation Number of deaths Duration of hospitalisation due to fever or respiratory illness Number of days of unplanned absenteeism for any reason Hospital-related health costs associated with participant hospitalisation Type and severity of local and systemic adverse event over the 3 months |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Netherlands |
Spain |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
LVLS This trial may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. Circumstances that may warrant termination or suspension include, but are not limited to: • Determination of an unexpected, significant, or unacceptable risk to participants that meets the definition of a SSI • Insufficient compliance • Data that are not sufficiently complete and/or evaluable • Demonstration of efficacy • Determination that the primary endpoint has been met |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |