VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including Coronavirus Disease 2019 in the Elderly: A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study

Abstract

Background Bacille Calmette–Guérin (BCG) vaccination can potentially reduce the rate of respiratory infections in vulnerable populations. This study evaluates the safety and efficacy of VPM1002 (a genetically modified BCG) as prophylaxis against severe respiratory tract infections including COVID-19 in an elderly population. Methods In this phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy elderly volunteers (n = 2064) were enrolled, randomized (1:1) to receive either VPM1002 or placebo, and followed up remotely for 240 days. The primary outcome was the mean number of days with severe respiratory infections at hospital and/or at home. Secondary endpoints included the incidence of self-reported fever, number of hospital and ICU admissions, and number of adverse events. Results A total of 31 participants in the VPM1002 group reported at least 1 day with severe respiratory disease and a mean number of days with severe respiratory disease of 9.39 ± 9.28 days while in the placebo group, 38 participants reported a mean of 14.29 ± 16.25 days with severe respiratory disease. The incidence of self-reported fever was lower in the VPM1002 group (odds ratio: 0.46; 95% CI: 0.28 to 0.74; p-value: 0.001) and consistent trends to less hospitalization and ICU admissions due to COVID-19 were observed after VPM1002-vaccination. Local reactions typical for BCG were observed in the VPM1002-vaccinated group, which were mostly of mild intensity. Conclusions Vaccination with VPM1002 is well tolerated and seems to have a prophylactic effect against severe respiratory diseases in the elderly. (ClinicalTrials.gov: NCT04435379)

Non-Specific Effects of Bacillus Calmette-Guérin: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The median number of participants per study was 1272 (interquartile range (IQR) 3072-265). Seven trials (44%) were conducted in newborn children [ 4 , 5 , 6 , 7 , 8 , 32 , 33 ], one (6%) in adolescents [ 34 ], three (19%) in adults [ 35 , 36 , 37 ], and four trials (25%) in elderly [ 16 , 38 , 39 , 40 ]. One trial (6%) included all age groups [ 41 ].…”

“…One trial (6%) included all age groups [ 41 ]. Eight trials (50%) mainly included Black participants [ 4 , 5 , 6 , 33 , 34 , 35 , 37 , 41 ], two trials (13%) mainly Asian participants [ 32 , 38 ], and six trials (38%) were conducted with participants of mainly Caucasian ethnicity [ 7 , 8 , 16 , 36 , 39 , 40 ]. Ten trials (63%) were conducted in healthy individuals [ 7 , 8 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 ], two (13%) included participants with various comorbidities [ 16 , 39 ], and four (25%) were done in low-birth-weight children (<2500 g) [ 4 , 5 , 6 , 32 ].…”

“…Eight trials (50%) mainly included Black participants [ 4 , 5 , 6 , 33 , 34 , 35 , 37 , 41 ], two trials (13%) mainly Asian participants [ 32 , 38 ], and six trials (38%) were conducted with participants of mainly Caucasian ethnicity [ 7 , 8 , 16 , 36 , 39 , 40 ]. Ten trials (63%) were conducted in healthy individuals [ 7 , 8 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 ], two (13%) included participants with various comorbidities [ 16 , 39 ], and four (25%) were done in low-birth-weight children (<2500 g) [ 4 , 5 , 6 , 32 ]. The primary objectives of 15 trials (94%) was to evaluate BCG-mediated NSE on mortality, infections of any origin, and respiratory infections [ 4 , 5 , 6 , 7 , 8 , 16 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]; five trials (31%) specifically investigated BCG-mediated NSE on COVID-19 [ …”

“…Ten trials (63%) were conducted in healthy individuals [ 7 , 8 , 33 , 34 , 35 , 36 , 37 , 38 , 40 , 41 ], two (13%) included participants with various comorbidities [ 16 , 39 ], and four (25%) were done in low-birth-weight children (<2500 g) [ 4 , 5 , 6 , 32 ]. The primary objectives of 15 trials (94%) was to evaluate BCG-mediated NSE on mortality, infections of any origin, and respiratory infections [ 4 , 5 , 6 , 7 , 8 , 16 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]; five trials (31%) specifically investigated BCG-mediated NSE on COVID-19 [ 16 , 35 , 36 , 37 , 40 ]; one (6%) trial was conducted to study prevention of Mycobacterium tuberculosis infection with BCG revaccination [ 34 ]. As intervention the BCG Denmark strain was used in ten trials (63%) [ 4 , 5 , 6 , 7 , 8 , 33 , 34 , 36 , 37 , 39 ]; one trial (6%) used the BCG Glaxo-strain which ...…”

“…The primary objectives of 15 trials (94%) was to evaluate BCG-mediated NSE on mortality, infections of any origin, and respiratory infections [ 4 , 5 , 6 , 7 , 8 , 16 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]; five trials (31%) specifically investigated BCG-mediated NSE on COVID-19 [ 16 , 35 , 36 , 37 , 40 ]; one (6%) trial was conducted to study prevention of Mycobacterium tuberculosis infection with BCG revaccination [ 34 ]. As intervention the BCG Denmark strain was used in ten trials (63%) [ 4 , 5 , 6 , 7 , 8 , 33 , 34 , 36 , 37 , 39 ]; one trial (6%) used the BCG Glaxo-strain which is genetically close to the BCG Denmark strain [ 41 ]; two trials (13%) used the BCG Moscow strain [ 16 , 37 ]; one trial (6%) used the strain VPM1002 [ 40 ]; the remaining two trials (13%) used the strains BCG Paris or BCG Russia, respectively [ 32 , 38 ]. Participants were reported to be naïve for BCG in seven trials (44%) [ 4 , 5 , 6 , 7 , 8 , 32 , 33 ].…”