1. 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.
- Author
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Blossey AM, Brückner S, May M, Parzmair GP, Sharma H, Shaligram U, Grode L, Kaufmann SHE, Netea MG, and Schindler C
- Subjects
- Aged, Humans, Double-Blind Method, Hospitalization statistics & numerical data, SARS-CoV-2, Respiratory Tract Diseases prevention & control, Middle Aged, Aged, 80 and over, Male, Female, Time Factors, Patient Acuity, BCG Vaccine immunology, BCG Vaccine standards, COVID-19 prevention & control
- 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 coronavirus disease 2019 (COVID-19) in an elderly population., Methods: In this phase 3, 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 intensive care unit (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 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% confidence interval, .28-.74]; P = .001), and consistent trends to fewer 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 disease in the elderly., Clinical Trials Registration: NCT04435379., Competing Interests: Potential conflicts of interest. H. S. and U. S. are employed by SIIPL, which manufactures VPM1002. L. G., A. M. B., S. B., M. M., and G. P. P. are employed by VPM, which developed the vaccine. S. H. E. K. and L. G. are coinventors and named patent holders for VPM1002, which is licensed to Vakzine Projekt Management, Hannover, Germany, and sublicensed to Serum Institute of India Pvt Ltd. S. H. E. K. is also coholder of a patent licensed to Serum Institute of India Pvt Ltd; reports consulting fees (honorarium) from Memo Therapeutics AG, Switzerland, LTS Lohmann Therapie-Systeme AG, Germany, kENUP Foundation, Malta, and TUI AG, Germany; honorarium from IPSEN for speaker activities (information event for IPSEN employees) and from Gilead for speaker activity; and a role as Chair of Board for Schering Foundation. S. B. reports royalties or licenses related to a patent planned issued or pending (TB vaccine VPM1002) as an employee of VPM, the patent holder. M. G. N. is a scientific founder of TTxD and Lemba. M. G. N. also reports unrestricted research grants from GSK, ViiV Healthcare, Ono Pharma, and TTxD, all awarded to institution; patents for nanobiologics inducing or inhibiting trained immunity; participation on a scientific advisory board for TTxD; and stock in TTxD. G. P. P. reports royalties or licences and patents planned, issued, or pending for TB vaccine VPM1002, as an employee of VPM, the patent holder. H. S. reports license held by Serum Institute of India Pvt Ltd. L. G. reports royalties or licences and patents planned, issued, or pending related to employment with VPM, the patent holder of TB vaccine VPM1002. C. S. reports participation in the blinded part of the data and safety monitoring board as principal investigator of the present trial (no advisory board). All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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