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This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) when administered at different dosages by different routes (intradermally, intranasally or intramuscularly) in healthy adults (18 to 45 years of age at enrollment). The safety profile of the 1790GAHB vaccine is evaluated in comparison to that of placebo (GAHB-Placebo), constituted by an aluminum hydroxide suspension having the same concentration as study vaccine formulations. A total of 52 eligible subjects will be assigned to one of three sequential cohorts as follows:
Cohort A) 0.1 μg ID and 5 μg IN Cohort B) 1 μg ID and 20 μg IN Cohort C) 10 μg ID, 80 μg IN and 5 μg IM Within each cohort, in an observer-blind fashion, subjects will be randomized to receive three vaccinations, four weeks apart, of either 1790GAHB vaccine (at five antigen concentrations) or GAHB placebo. Specifically for IN and ID administration routes, a Data Safety Monitoring Board will be in place to receive a summary of all safety data obtained during one week follow-up post-first vaccination with the lower dose. Based on evaluation of the safety data, the Data Safety Monitoring Board will make a recommendation, as to whether the next cohort should be vaccinated with higher antigen concentration or not.
Expected duration of the study for an individual subject is 9 months. Each subject will be followed-up for 6 months after the 3rd vaccination
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| S. sonnei 1790GAHB - 0.1 mcg - ID | Experimental | Subjects enrolled in COHORT A receiving 3 injections of S. sonnei 1790GAHB - 0.1 mcg intradermally (ID) |
|
| S. sonnei 1790GAHB - 1 mcg - ID | Experimental | Subjects enrolled in COHORT B receiving 3 injections of S. sonnei 1790GAHB - 1 mcg intradermally (ID) |
|
| S. sonnei 1790GAHB - 10 mcg - ID | Experimental | Subjects enrolled in COHORT C receiving 3 injections of S. sonnei 1790GAHB - 10 mcg intradermally (ID) |
|
| S. sonnei 1790GAHB - 5 mcg - IN | Experimental | Subjects enrolled in COHORT A receiving 3 injections of S. sonnei 1790GAHB - 5 mcg intranasally (IN) |
|
| S. sonnei 1790GAHB - 20 mcg - IN | Experimental | Subjects enrolled in COHORT B receiving 3 injections of S. sonnei 1790GAHB - 20 mcg intranasally (IN) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| S. sonnei 1790GAHB | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with solicited local reaction after any vaccination | Any erythema/induration/swelling refers to: ≥25 mm in diameter. Grade 3 (severe) refers to erythema/induration/swelling >100 mm in diameter. Grade 3 (severe) for injection site pain/nasal pain/facial edema/rhinorrhea refers to: prevents daily activity | During a 7-day (Days 1-7) post vaccination period following any injection |
| Number of subjects with solicited systemic reaction after any vaccination | Any= Incidence of any symptom regardless of intensity grade. Grade 3 = symptom that prevented daily activities | During a 7-day (Days 1 to 7) post vaccination period following any injection |
| Number of subjects with Neutrophils results below and above the normal ranges | Day 8: VISIT 2 (D7 post 1st vac) | At Day 8 |
| Number of subjects with Neutrophils results below and above the normal | Day 36: VISIT 3.1 (D7 post 2nd vac) | At Day 36 |
| Number of subjects with Neutrophils results below and above the normal | Day 57: VISIT 4 (3rd vac.) | At Day 57 |
| Number of subjects with Neutrophils results below and above the normal | Day 64: VISIT 4.1 (D7 post 3rd vac.) | At Day 64 |
| Number of subjects with Neutrophils results below and above the normal |
| Measure | Description | Time Frame |
|---|---|---|
| Anti-LPS S. sonnei serum IgG Geometric mean concentration (GMCs) | At baseline, at 28 days after each vaccination and at 168 days after last vaccination | |
| Number of subjects with seroresponse for anti-LPS S. sonnei | Seroresponse is defined as: If half of the baseline value is greater than 25 ELISA Unit (EU) then an increase of at least 50% in the post-vaccination sample as compared to baseline [i.e. ((Post-vac minus baseline)/baseline)100% ≥ 50%]. If half of the baseline value is less or equal to 25 EU then an increase of at least 25 EU in the post-vaccination sample as compared to baseline (i.e. [post-vac minus baseline] ≥25 EU) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David JM Lewis, MD | University of Surrey, Guildford, GU2 7XP United Kingdom | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Surrey Clinical Research Center (Surrey CRC) | Guildford | Surrey | GU2 7XP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28735965 | Derived | Launay O, Lewis DJM, Anemona A, Loulergue P, Leahy J, Scire AS, Maugard A, Marchetti E, Zancan S, Huo Z, Rondini S, Marhaba R, Finco O, Martin LB, Auerbach J, Cohen D, Saul A, Gerke C, Podda A. Safety Profile and Immunologic Responses of a Novel Vaccine Against Shigella sonnei Administered Intramuscularly, Intradermally and Intranasally: Results From Two Parallel Randomized Phase 1 Clinical Studies in Healthy Adult Volunteers in Europe. EBioMedicine. 2017 Aug;22:164-172. doi: 10.1016/j.ebiom.2017.07.013. Epub 2017 Jul 15. | |
| 27490698 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 6, 2017 | |
| Reset | May 29, 2018 | |
| Release | Aug 10, 2018 | |
| Reset | Jan 22, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 6, 2017 | May 29, 2018 | |||
| Aug 10, 2018 |
| ID | Term |
|---|---|
| D004405 | Dysentery, Bacillary |
| ID | Term |
|---|---|
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| S. sonnei 1790GAHB - 80 mcg - IN |
| Experimental |
Subjects enrolled in COHORT C receiving 3 injections of S. sonnei 1790GAHB - 80 mcg intranasally (IN) |
|
| S. sonnei 1790GAHB - 5 mcg - IM | Experimental | Subjects enrolled in COHORT C receiving 3 injections of S. sonnei 1790GAHB - 5 mcg intramuscularly (IM) |
|
| Placebo - ID | Placebo Comparator | 2 subjects enrolled in each COHORT A, B and C receiving 3 injections of Placebo intradermally (ID). These were pooled in one Placebo group in the analyses |
|
| Placebo - IN | Placebo Comparator | 2 subjects enrolled in each COHORT A, B and C receiving 3 injections of Placebo intranasally (IN). These were pooled in one Placebo group in the analyses |
|
| Placebo - IM | Placebo Comparator | 2 subjects enrolled in COHORT C receiving 3 injections of Placebo intramuscularly (IM) |
|
|
| Placebo | Biological |
|
Day 85: VISIT 5 (1 month post 3rd vac.)
| At Day 85 |
| Number of subjects with Neutrophils results below and above the normal | Day 225: VISIT 6 (6 months post 3rd vac.) | At Day 225 |
| At 28 days after each vaccination and 168 days after last vaccination |
| Number of subjects with high seroresponse for anti-LPS S. sonnei (IgG ELISA ≥121 EU) | High seroresponse is defined as a post vaccination titer ≥X anti-LPS serum IgG units in the GSK (former Novartis) ELISA that correspond to a titer of 1:800 in the ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). To determine the value for 'X' the GSK (former Novartis) anti-LPS ELISA was calibrated against the Cohen ELISA and it was found that a concentration of 121 EU EU/mL corresponds to a titer of 1:800 in the Cohen assay | At baseline, at 28 days after each vaccination and at 168 days after last vaccination |
| Derived |
| Muturi-Kioi V, Lewis D, Launay O, Leroux-Roels G, Anemona A, Loulergue P, Bodinham CL, Aerssens A, Groth N, Saul A, Podda A. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review. PLoS One. 2016 Aug 4;11(8):e0157385. doi: 10.1371/journal.pone.0157385. eCollection 2016. |
| Jan 22, 2019 |
| D007239 | Infections |
| D004403 | Dysentery |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |