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| ID | Type | Description | Link |
|---|---|---|---|
| 75A50122C00028 | Other Grant/Funding Number | Health and Human Services and Biomedical Advanced Research and Development Authority | |
| WT224842 | Other Grant/Funding Number | Wellcome Trust | |
| Agmt dtd 2/28/2023 | Other Grant/Funding Number | UK Department of Health and Social Care as part of the Global Antimicrobial Resistance Innovation Fund | |
| Agmt dtd 1/30/2023 | Other Grant/Funding Number | Germany's Federal Ministry of Education and Research |
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| Name | Class |
|---|---|
| Biomedical Advanced Research and Development Authority | FED |
| Wellcome Trust | OTHER |
| Navy Medical Research Command (NMRC) | UNKNOWN |
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In this study, the candidate vaccine LTB-SA7 will be tested for safety and immunogenicity in healthy adults.
LTB-SA7 is a candidate vaccine designed to induce immune response against toxins produced by Staphylococcus aureus. During the study, healthy adults will be randomized to receive one out of three different vaccine doses (starting with the group receiving the lowest dose), or a placebo. Participants will receive 2 injections, either two with candidate vaccine, 1 vaccine and 1 placebo, or 2 times placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LTB-SA7 low dose, 1 vaccination | Experimental | The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo. |
|
| LTB-SA7 low dose, 2 vaccinations | Experimental | The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart. |
|
| LTB-SA7 medium dose, 1 vaccination | Experimental | The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo. |
|
| LTB-SA7 medium dose, 2 vaccinations | Experimental | The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart. |
|
| LTB-SA7 high dose, 1 vaccination | Experimental | The candidate toxoid vaccine (LTB-SA7) is administered once, 1 month later participant receives a placebo. |
|
| LTB-SA7 high dose, 2 vaccinations |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LTB-SA7 | Biological | LTB-SA7 is a toxoid based vaccine consisting of five components including seven toxoids formulated with Alhydrogel. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety - Solicited local and systemic AEs | Occurrence and severity of solicited local and systemic AEs during 7 days after each dose (i.e., day of vaccination and the 6 subsequent days) in all participants by intervention group. | During 7 days following each vaccination. |
| Safety - Unsolicited AEs | Occurrence, severity, and relationship to vaccination of unsolicited AEs during 28 days after each dose (i.e., day of injection and the 27 subsequent days) in all participants by intervention group. | During 28 days following each vaccination. |
| Safety - SAEs | Occurrence, severity, and relationship to vaccination of SAEs in all participants during the trial duration by intervention group. | Throughout the study, on average 8 months |
| Immunogenicity - GMTs of anti-toxoids IgGs in serum at V4 | Serum IgG antibody geometric mean titers (GMT) against each of the 7 toxoids present in the LTB-SA7 vaccine in serum samples collected 4 weeks after the 1st vaccination (Visit 4 [Day 29]) by intervention group to identify preferred dose(s). | 1 month from the first vaccination. |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity - GMTs of anti-toxoid IgGs in serum at V3, V5 and V6 | Serum IgG antibody geometric mean titers (GMT) against each of the 7 toxoids present in the LTB-SA7 vaccine in samples collected 1 week after 1st and 2nd vaccination and 4 weeks after 1st and 2nd vaccination (Visit 3 [Day 8], Visit 5 [Day 36], and Visit 6 [Day 57]). | From 1 week after first vaccination till Day 57 (Visit 6). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nehkonti Adams, MD | Naval Medical Research Command | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Naval Medical Research Command Clinical Trial Center | Bethesda | Maryland | 20889 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38274114 | Background | Schoergenhofer C, Gelbenegger G, Hasanacevic D, Schoner L, Steiner MM, Firbas C, Buchtele N, Derhaschnig U, Tanzmann A, Model N, Larcher-Senn J, Drost M, Eibl MM, Roetzer A, Jilma B. A randomized, double-blind study on the safety and immunogenicity of rTSST-1 variant vaccine: phase 2 results. EClinicalMedicine. 2024 Jan 5;67:102404. doi: 10.1016/j.eclinm.2023.102404. eCollection 2024 Jan. | |
| 16428778 |
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| Experimental |
The candidate toxoid vaccine (LTB-SA7) is administered twice, 1 month apart. |
|
| Placebo | Placebo Comparator | Participant receives placebo twice, 1 month apart. |
|
| Placebo | Biological | Sodium Phosphate with Sodium Chloride |
|
| Immunogenicity - GMFR of anti-toxoid IgGs in serum at V2-V6. | Serum IgG antibody geometric mean fold ratio (GMFR) vs. baseline. | Between baseline on Visit 2 (Day 1) until 4 weeks post 2nd vaccination on Visit 6 (Day 57). |
| Immunogenicity - Total IgGs titer in serum | Percentage of participants with ≥ 2-fold ≥ 4-fold, and ≥ 8-fold IgG titer increase vs. baseline. | Between baseline on Visit 2 (Day 1) until 4 weeks post 2nd vaccination on Visit 6 (Day 57). |
| Background |
| Rajagopalan G, Iijima K, Singh M, Kita H, Patel R, David CS. Intranasal exposure to bacterial superantigens induces airway inflammation in HLA class II transgenic mice. Infect Immun. 2006 Feb;74(2):1284-96. doi: 10.1128/IAI.74.2.1284-1296.2006. |
| 17606031 | Background | Nizet V. Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets. J Allergy Clin Immunol. 2007 Jul;120(1):13-22. doi: 10.1016/j.jaci.2007.06.005. |
| 22670044 | Background | Tattevin P, Schwartz BS, Graber CJ, Volinski J, Bhukhen A, Bhukhen A, Mai TT, Vo NH, Dang DN, Phan TH, Basuino L, Perdreau-Remington F, Chambers HF, Diep BA. Concurrent epidemics of skin and soft tissue infection and bloodstream infection due to community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2012 Sep;55(6):781-8. doi: 10.1093/cid/cis527. Epub 2012 Jun 5. |
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| 26836234 | Background | Tree JA, Hall G, Rees P, Vipond J, Funnell SG, Roberts AD. Repeated high-dose (5 x 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits. Hum Vaccin Immunother. 2016 Jul 2;12(7):1795-801. doi: 10.1080/21645515.2015.1134070. |
| 17540252 | Background | Tristan A, Ferry T, Durand G, Dauwalder O, Bes M, Lina G, Vandenesch F, Etienne J. Virulence determinants in community and hospital meticillin-resistant Staphylococcus aureus. J Hosp Infect. 2007 Jun;65 Suppl 2:105-9. doi: 10.1016/S0195-6701(07)60025-5. |
| 30824769 | Background | Venkatasubramaniam A, Adhikari RP, Kort T, Liao GC, Conley S, Abaandou L, Kailasan S, Onodera Y, Krishnan S, Djagbare DM, Holtsberg FW, Karauzum H, Aman MJ. TBA225, a fusion toxoid vaccine for protection and broad neutralization of staphylococcal superantigens. Sci Rep. 2019 Mar 1;9(1):3279. doi: 10.1038/s41598-019-39890-z. |
| 33717122 | Background | Venkatasubramaniam A, Liao G, Cho E, Adhikari RP, Kort T, Holtsberg FW, Elsass KE, Kobs DJ, Rudge TL Jr, Kauffman KD, Lora NE, Barber DL, Aman MJ, Karauzum H. Safety and Immunogenicity of a 4-Component Toxoid-Based Staphylococcus aureus Vaccine in Rhesus Macaques. Front Immunol. 2021 Feb 25;12:621754. doi: 10.3389/fimmu.2021.621754. eCollection 2021. |
| 30782986 | Background | Verreault D, Ennis J, Whaley K, Killeen SZ, Karauzum H, Aman MJ, Holtsberg R, Doyle-Meyers L, Didier PJ, Zeitlin L, Roy CJ. Effective Treatment of Staphylococcal Enterotoxin B Aerosol Intoxication in Rhesus Macaques by Using Two Parenterally Administered High-Affinity Monoclonal Antibodies. Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02049-18. doi: 10.1128/AAC.02049-18. Print 2019 May. |
| 17109350 | Background | Voyich JM, Otto M, Mathema B, Braughton KR, Whitney AR, Welty D, Long RD, Dorward DW, Gardner DJ, Lina G, Kreiswirth BN, DeLeo FR. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? J Infect Dis. 2006 Dec 15;194(12):1761-70. doi: 10.1086/509506. Epub 2006 Nov 2. |
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