Brief Title: BCG Vaccination to Prevent COVID-19

INTRODUCTION

• Org Study ID: USUHS.2020-062
• Secondary ID: N/A
• NTC ID: NCT04632537
• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

BRIEF SUMMARY

The current COVID-19 epidemic threatens to overwhelm the capacity of many countries to meet
their populations' health care needs. Although several vaccines specific for SARS-CoV-2 have
been or are being developed, these require testing in animal and human safety studies and
they are unlikely to be available during the expected peak periods of the growing epidemic.
Two groups at especially high risk of infection and disease are front line health care
workers working directly with COVID-19 patients and elderly residents of group homes or
facilities that provide skilled nursing care to this frail population. Interim measures to
protect these groups while we await a high efficacy vaccine are desperately needed.

Based on the capacity of BCG to (1) reduce the incidence of respiratory tract infections in
children and adults; (2) exert antiviral effects in experimental models; and (3) reduce
viremia in an experimental human model of viral infection, we hypothesize that BCG
vaccination may induce (partial) protection against susceptibility to and/or severity of
SARS-CoV-2 infection.

This study will evaluate the efficacy of BCG to reduce risk of infection by SARS-CoV-2 and
mitigate COVID-19 disease severity in at risk health care providers.

A phase III randomized controlled trial provides the highest validity to answer this research
question. Given the immediate threat of the SARS-CoV-2 epidemic the trial has been designed
as a pragmatic study with a highly feasible primary endpoint, which can be continuously
measured. This allows for the most rapid identification of a beneficial outcome that would
allow other at-risk individuals, including the control population, to also benefit from the
intervention if and as soon as it has demonstrated efficacy and safety.

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DETAILED DESCRIPTION

This study is a multi-center, prospective, double-blind, randomized placebo-controlled trial
to assess the efficacy of intradermal TICE BCG (for intravesical use, Merck) BCG LIVE or
placebo vaccine, in reducing the incidence of infection of SARS-CoV2 and severity of COVID-19
disease. This study proposes to examine BCG-induced nonspecific trained immunity to provide
protection from SARS-CoV2 among health care workers who are likely to care for patients with
COVID-19 illness, 18-64 years of age.

Up to 670 individuals will be screened to enroll 550 participants with a planned 50 person
enrollment at USU site, 300 persons at Darnall Medical Center (CRDMC) and 200 persons at
Brooke Army Medical Center (BAMC), resulting in 275 receiving BCG vaccine and 275 receiving
placebo. To account for attrition prior to vaccination we will enroll up to 70 at USU, up to
350 at CRDMC and up to 250 at BAMC.

There are three phases in which research procedures will be completed: (1) initial screening
for eligibility, consent, baseline testing; (2) enrollment, randomization, if pertains- prior
to vaccination research blood draw for peripheral blood mononuclear cells (PBMC), and
immunization with study vaccine (BCG or placebo); and (3) follow-up screening and testing.

Participants will be followed to assess whether infection with SARS-CoV-2 occurs:

Participants will complete intermittent surveys via an electronic system every 2 weeks to
assess the presence of any flu-like symptom. Any positive response on the survey will trigger
a nasopharyngeal swab to be collected to test for COVID-19 via rt-PCR.

All participants, regardless of survey responses, will have serology (4mL SST tube) for
COVID-19 tested at monthly intervals during the 6 month follow-up period or until a positive
test result occurs.

If a participant completes the follow-up period and does not test positive for COVID disease,
study participation is complete.

If a participant does test positive for COVID-19 disease at any point during follow-up,
disease status will be ascertained for up to two months from the time of positive test or
until an outcome is available through one of the following mechanisms:

(1) an electronic survey if not admitted to the hospital, including questions about the
number of days ill, daily fever, and other symptoms; or (2) if admitted to the hospital,
ordinal outcomes for disease severity will be extracted from the hospital's medical records
system for the 2 month period of highest acuity. Participants will have a final study visit
after hospitalization when cleared for outpatient follow up.

During the first 6 weeks of follow-up post vaccination, all participants will be asked about
any adverse events; thereafter, participants will report vaccine-related and solicited
adverse events (AE), as well as unsolicited AEs through the electronic survey.

• Overall Status
  Recruiting
• Start Date
  December 7, 2020
• Phase
  Phase 3
• Study Type
  Interventional