Active clinical trials for "Dysentery, Bacillary"

The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the GSK3536852A vaccine, which was designed to protect against shigellosis caused by Shigella sonnei (S. sonnei) and is using the new Generalized Modules for Membrane Antigens (GMMA) platform technology developed by GlaxoSmithKline (GSK) Vaccines Institute for Global Health (GVGH). The study vaccine could be the stepping stone for the development of a multivalent broadly protective Shigella vaccine for vaccination of impoverished communities where shigellosis is endemic. However, a standalone monovalent vaccine against S. sonnei could be used to protect travelers against diarrheal shigellosis, as the vast majority of travelers' shigellosis is caused by S. sonnei, and even to protect infants in endemic regions where shigellosis is primarily caused by S. sonnei. The GSK3536852A vaccine has been tested in two Phase I dose escalation studies in Europe to assess its safety and immunogenicity via three routes of administration: intramuscular (IM), intranasal (IN) and intradermal (ID). The results from the first study (dose escalation with IM vaccination) have shown that the vaccine has an acceptable safety profile and is well-tolerated up to a dose of 100 micrograms (µg). The results from the second study (dose escalation with ID, IN and IM vaccination) showed that GSK3536852A vaccine is well-tolerated also when administered by the ID and IN routes of vaccination. However, immunogenicity data have shown that GSK3536852A vaccine administered by the ID and IN routes is not as immunogenic as GSK3536852A vaccine administered by the IM route. Therefore, it has been decided to proceed with the clinical development program of this vaccine only using the IM vaccination route. In terms of dosage, the regimen tested in Phase I studies (three doses given one month apart) did not show any significant benefit from the third dose in terms of immunogenicity, therefore a two dose schedule was selected for next studies. A Phase IIa study, conducted in endemic regions of Africa (i.e., Kenya), has been completed and confirmed the acceptable safety profile and immunogenicity of GSK3536852A vaccine. Performing this vaccine-human challenge study may give the opportunity to establish evidence of clinical protection induced by the candidate S. sonnei vaccine (GSK3536852A vaccine) at an early development stage.

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

Phase 1, randomized, double-blind, placebo controlled, dose-escalation, inpatient study of single doses of S. sonnei. Health adult subjects, ranging in age from 18 to 45 years of age (inclusive) will be screened. Enroll serial groups up to 90 subjects. The primary objective is to evaluate safety and tolerance of WRSs2 by monitoring presence, frequency and severity of clinical signs and symptoms. A secondary objective is to evaluate the immune response in blood and stool following ingestion of WRSs2 and WRSs3.

This study is an inpatient trial to determine the safety, immunogenicity and efficacy of the WRSS1 candidate vaccine in healthy Thai adult volunteers.

Healthy volunteers will receive a 2-dose vaccination with Shigella dysenteriae candidate vaccine spaced 8 weeks apart. The objective is to demonstrate the safety and reactogenicity of the Shigella dysenteriae bioconjugate vaccine (GVXN SD133) alone or in combination with an adjuvant (Aluminium Hydroxide). The safety and reactogenicity of the GVXN SD133 vaccine will be also evaluated at two different concentrations of antigen, Shigella polysaccharide O1. Blood samples will be collected at intervals to examine systemic vaccine antigen-specific immune responses.

This study is an open-label, dose-escalating Phase 1 investigation of S. flexneri 2a InvaplexAR vaccine. A total of up to 40 subjects will receive one of four S. flexneri 2a InvaplexAR vaccine doses. The vaccine will be administered intranasally (without adjuvant).

This Phase 1 clinical trial is aimed to evaluate the safety and immunogenicity of 3 doses of 5 sequentially escalating dosages of a candidate vaccine against Shigella sonnei (1790GAHB vaccine) administered by intramuscular route 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 50 eligible subjects will be assigned to one of five sequential cohorts of 10 subjects each. 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. 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.

Shigellosis remains a serious and frequent disease throughout the world. Development of vaccines has been difficult because shigellae are habitants of and pathogens for humans only and there is no consensus about the mechanism(s) of immunity to this pathogen. Incomplete, but compelling evidence, indicates that a critical level of serum IgG anti-LPS confers immunity to shigellosis. Important data come from our clinical trial in the Israel Defense Forces (IDF) recruits. A randomized, double-blind, vaccine-controlled study showed that the S. sonnei-rEPA elicited 74% protection against shigellosis occurring about 3 months after vaccination (p=0.001). This vaccine conferred 43% (p=0.04) protection in one company during an outbreak up to 14 days following vaccination suggesting that our Shigella conjugates might be of value in epidemics. The efficacy of S. sonnei-rEPA was correlated with the level of vaccine-induced IgG antibodies. The highest incidence, morbidity, and mortality of shigellosis is in young children. But serum antibody responsiveness to polysaccharide-based vaccines is age-dependent and infants and young children respond poorly or not at all to both disease and vaccination. The safety and immunogenicity of these Shigella conjugates in 4 to 6 years-old children in Israel was demonstrated. But although the fold rise in anti-LPS was similar in the children, the level of anti-LPS elicited by the conjugates was lower than in adults. We improved the immunogenicity of Shigella conjugates as shown in mice and then in adult humans. Now we apply to evaluate the safety, immunogenicity and efficacy of these improved conjugates in 1 to 4 years-old children in Israel. In Israel, shigellosis is common especially in children. S. sonnei (Group D) comprise about 60% of the isolates followed by S. flexneri (Group B): Shigella dysenteriae type 1 (Group A) is not found. We propose to administer 2 injections of either S. sonnei-CRM9 or S. flexneri type 2a-rEPAsucc 6 weeks apart in a random double-blind fashion to about 6,000 1 to 4 year-olds. Active surveillance of the vaccinees for enteric infections will be maintained for at least 2 years to evaluate the effect of vaccination.

GVGH Shigella Sonnei 1970GAHB is a vaccine aimed at preventing the disease caused by Shigella sonnei. A post-hoc analysis of subjects who participated in the parent study showed significantly different responses in subjects with detectable versus undetectable antibody titres at baseline, suggesting the possibility that the vaccine might not be sufficiently immunogenic in completely naïve adults. This study was then designed to further characterize the immunogenicity profile of the vaccine and to evaluate whether it was able to induce an immunological memory response.

In this study, the tetravalent bioconjugate candidate vaccine Shigella4V will be tested to obtain first-in-human data on its safety and immunogenicity in infants and to identify the preferred dose of Shigella4V in 9 month old infants.