Nctid:
NCT06615375
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-12-20"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D004405", "term"=>"Dysentery, Bacillary"}], "ancestors"=>[{"id"=>"D004756", "term"=>"Enterobacteriaceae Infections"}, {"id"=>"D016905", "term"=>"Gram-Negative Bacterial Infections"}, {"id"=>"D001424", "term"=>"Bacterial Infections"}, {"id"=>"D001423", "term"=>"Bacterial Infections and Mycoses"}, {"id"=>"D007239", "term"=>"Infections"}, {"id"=>"D004403", "term"=>"Dysentery"}, {"id"=>"D005759", "term"=>"Gastroenteritis"}, {"id"=>"D005767", "term"=>"Gastrointestinal Diseases"}, {"id"=>"D004066", "term"=>"Digestive System Diseases"}, {"id"=>"D007410", "term"=>"Intestinal Diseases"}], "browseLeaves"=>[{"id"=>"M7579", "name"=>"Dysentery, Bacillary", "asFound"=>"Shigellosis", "relevance"=>"HIGH"}, {"id"=>"M7577", "name"=>"Dysentery", "relevance"=>"LOW"}, {"id"=>"M10283", "name"=>"Infections", "relevance"=>"LOW"}, {"id"=>"M6368", "name"=>"Communicable Diseases", "relevance"=>"LOW"}, {"id"=>"M7918", "name"=>"Enterobacteriaceae Infections", "relevance"=>"LOW"}, {"id"=>"M4722", "name"=>"Bacterial Infections", "relevance"=>"LOW"}, {"id"=>"M19249", "name"=>"Gram-Negative Bacterial Infections", "relevance"=>"LOW"}, {"id"=>"M12136", "name"=>"Mycoses", "relevance"=>"LOW"}, {"id"=>"M4721", "name"=>"Bacterial Infections and Mycoses", "relevance"=>"LOW"}, {"id"=>"M8875", "name"=>"Gastroenteritis", "relevance"=>"LOW"}, {"id"=>"M8883", "name"=>"Gastrointestinal Diseases", "relevance"=>"LOW"}, {"id"=>"M7255", "name"=>"Digestive System Diseases", "relevance"=>"LOW"}, {"id"=>"M10444", "name"=>"Intestinal Diseases", "relevance"=>"LOW"}, {"id"=>"T5205", "name"=>"Shigellosis", "asFound"=>"Shigellosis", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Infections", "abbrev"=>"BC01"}, {"name"=>"Digestive System Diseases", "abbrev"=>"BC06"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"browseLeaves"=>[{"id"=>"M17360", "name"=>"Vaccines", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"RANDOMIZED", "maskingInfo"=>{"masking"=>"QUADRUPLE", "whoMasked"=>["PARTICIPANT", "CARE_PROVIDER", "INVESTIGATOR", "OUTCOMES_ASSESSOR"]}, "primaryPurpose"=>"PREVENTION", "interventionModel"=>"PARALLEL"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>120}}, "statusModule"=>{"overallStatus"=>"RECRUITING", "startDateStruct"=>{"date"=>"2024-11-12", "type"=>"ACTUAL"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-11", "completionDateStruct"=>{"date"=>"2025-12", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-11-15", "studyFirstSubmitDate"=>"2024-09-20", "studyFirstSubmitQcDate"=>"2024-09-24", "lastUpdatePostDateStruct"=>{"date"=>"2024-11-19", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-09-26", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2025-10", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"To demonstrate that the Shigella4V2 bioconjugate vaccine protects against shigellosis following challenge with the wild type S. sonnei 53G strain.", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"The number of challenged participants with shigellosis post-challenge during the inpatient period that received vaccine compared to participants who received placebo. Shigellosis is defined as:\n\n1. Severe diarrhea; OR\n2. Moderate diarrhea AND \\[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\\]; OR\n3. Dysentery AND \\[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\\]"}], "secondaryOutcomes"=>[{"measure"=>"Efficacy - Number of participants with moderate-to-severe shigellosis", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of moderate-to-severe shigellosis post-challenge during the inpatient period. Moderate-to-severe shigellosis is defined as:\n\n1. Moderate or severe diarrhea AND \\[fever OR ≥ 1 severe constitutional/enteric symptoms OR ≥ 3 episodes of vomiting in 24 h\\]; OR\n2. Dysentery AND \\[fever OR ≥ 1 severe constitutional/enteric symptoms OR ≥ 3 episodes of vomiting in 24 h\\]"}, {"measure"=>"Efficacy - Number of participants with diarrhea of any severity", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of ≥ 2 loose stools in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with severe diarrhea", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of ≥ 6 loose stools or more than 800 g of stool in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with moderate or severe diarrhea", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of ≥ 4 loose stools or ≥ 400 g of stool in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with more severe diarrhea", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of ≥ 10 loose stools or ≥ 1000 g of stool in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Maximum weight of grade 3-5 stools passed in 24 h per participant", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Maximum weight of loose stools (grade 3-5) passed in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Maximum number of grade 3-5 stools passed in 24 h per participant", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Maximum number of loose stools (grade 3-5) passed in any 24-hour period post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with moderate or severe constitutional enteric symptoms", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of moderate or severe constitutional enteric symptoms post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with severe constitutional enteric symptoms", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of severe constitutional enteric symptoms post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with fever", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of fever post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Highest recorded temperature", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Highest recorded temperature post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Time from challenge to onset of diarrhea", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Time (in hours) from challenge to first loose stool that contributes to diarrhea (≥ 2 loose stools in a 24-hour period)"}, {"measure"=>"Efficacy - Time from challenge to onset of shigellosis", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Time (in hours) from challenge to first event (e.g., first loose stool, first day of fever or moderate symptom, or first episode of vomiting) that contributes to the shigellosis endpoint"}, {"measure"=>"Efficacy - Duration of diarrhea", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Duration will be calculated as the time (in hours) from the first stool that contributes to diarrhea until the last stool that contributes to diarrhea, occurring post-challenge during the inpatient period, irrespective of intermittent time without loose stools"}, {"measure"=>"Efficacy - Shigella disease severity score", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Shigella disease severity score (scale from 0 to 9) post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants requiring early antibiotic therapy", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Receipt of antibiotic therapy prior to 5 days after challenge"}, {"measure"=>"Efficacy - Number of participants requiring IV fluids", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Receipt of IV fluids post-challenge during the inpatient period"}, {"measure"=>"Efficacy - Number of participants with blood in stool as confirmed by hemoccult", "timeFrame"=>"To be evaluated post-challenge during the inpatient period (Day 29 through Day 37) in vaccinees vs. placebo", "description"=>"Occurrence of at least one stool with blood as confirmed by hemoccult post-challenge during the inpatient period"}, {"measure"=>"Safety - Solicited Local and Systemic Adverse Events (AEs)", "timeFrame"=>"To be evaluated after injection in vaccinees vs. placebo during the 7-day follow-up period post-injection (day of administration and 6 following days)", "description"=>"Number of participants with solicited AEs, including local and general post-injection"}, {"measure"=>"Safety - Unsolicited AEs", "timeFrame"=>"To be evaluated after injection in vaccinees vs. placebo during the 28-day follow-up period post-injection (day of administration and 27 following days)", "description"=>"Number of participants with unsolicited AEs post-injection"}, {"measure"=>"Safety - All Solicited and Unsolicited AEs post-injection", "timeFrame"=>"To be evaluated after injection in vaccinees vs. placebo during the 28-day follow-up period post-injection (day of administration and 27 following days)", "description"=>"Number of participants with any AEs post-injection"}, {"measure"=>"Safety - Unsolicited AEs post-challenge", "timeFrame"=>"To be evaluated after challenge in vaccinees vs. placebo during the 28-day follow-up period post-challenge (day of challenge and 27 following days)", "description"=>"Number of participants with unsolicited AEs post-challenge"}, {"measure"=>"Safety - Medically relevant AEs", "timeFrame"=>"To be evaluated in vaccinees vs. placebo from 28 days post-injection (Day 29) or post-challenge (Day 57) until study end", "description"=>"Number of participants with medically relevant AEs"}, {"measure"=>"Safety - Serious Adverse Events (SAEs)", "timeFrame"=>"To be evaluated after injection in vaccinees vs. placebo until study end", "description"=>"Number of participants with SAEs"}, {"measure"=>"Safety - AEs leading to withdrawal from the trial", "timeFrame"=>"To be evaluated after injection in vaccinees vs. placebo until study end", "description"=>"Number of participants with AEs leading to withdrawal from the trial"}, {"measure"=>"Safety - Evaluate changes in hematological and blood chemistry parameters following injection", "timeFrame"=>"To be evaluated at 7-days post-injection compared to baseline values in vaccinees vs. placebo", "description"=>"Number of participants with hematological and blood chemistry laboratory abnormalities"}, {"measure"=>"Immunogenicity - Geometric mean titers (GMTs) of anti-S. sonnei LPS IgGs in serum", "timeFrame"=>"To be evaluated in vaccinees vs. placebo from Day 1 until study end", "description"=>"Anti-S. sonnei LPS IgG titer in serum collected at V1, V2, V3, V4 and V5 in Step 1, and at V1, V2, C-1, C8, and V4 in Step 2"}, {"measure"=>"Immunogenicity - GMTs of anti-S. flexneri 2a LPS IgGs in serum", "timeFrame"=>"To be evaluated in vaccinees vs. placebo from Day 1 until study end", "description"=>"Anti-S. flexneri 2a LPS IgG titer in serum collected at V1, V2, V3, V4 and V5 in Step 1, and at V1, V2, C-1, C8, and V4 in Step 2"}, {"measure"=>"Immunogenicity - GMTs of anti-S. flexneri 3a LPS IgGs in serum", "timeFrame"=>"To be evaluated in vaccinees vs. placebo from Day 1 until study end", "description"=>"Anti-S. flexneri 3a LPS IgG titer in serum collected at V1, V2, V3, V4 and V5 in Step 1, and at V1, V2, C-1, C8, and V4 in Step 2"}, {"measure"=>"Immunogenicity - GMTs of anti-S. flexneri 6 LPS IgGs in serum", "timeFrame"=>"To be evaluated in vaccinees vs. placebo from Day 1 until study end", "description"=>"Anti-S. flexneri 6 LPS IgG titer in serum collected at V1, V2, V3, V4 and V5 in Step 1, and at V1, V2, C-1, C8, and V4 in Step 2"}, {"measure"=>"Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of shigellosis", "timeFrame"=>"To be evaluated in challenged vaccinees from Day 1 to Day 37", "description"=>"Association between the primary shigellosis outcome and each of the following:\n\n* Serum anti-S. sonnei LPS IgG titer at C-1 (pre-challenge)\n* Maximum post-vaccination serum anti-S. sonnei LPS IgG titer through C-1 (pre-challenge)\n* Fold change from V1 (baseline) to C-1 (pre-challenge) in serum anti-S. sonnei LPS IgG titer"}, {"measure"=>"Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of moderate-to-severe shigellosis", "timeFrame"=>"To be evaluated in challenged vaccinees from Day 1 to Day 37", "description"=>"Association between moderate-to-severe shigellosis and each of the following:\n\n* Serum anti-S. sonnei LPS IgG titer at C-1 (pre-challenge)\n* Maximum post-vaccination serum anti-S. sonnei LPS IgG titer through C-1 (pre-challenge)\n* Fold change from V1 (baseline) to C-1 (pre-challenge) in serum anti-S. sonnei LPS IgG titer"}, {"measure"=>"Immunogenicity - establish or confirm immunomarker that correlate with a reduced risk of solicited events", "timeFrame"=>"To be evaluated in challenged vaccinees from Day 1 to Day 37", "description"=>"Association between the occurrence (any severity) and severity of each solicited event following challenge and each of the following:\n\n* Serum anti-S. sonnei LPS IgG titer at C-1 (pre-challenge)\n* Maximum post-vaccination serum anti-S. sonnei LPS IgG titer through C-1 (pre-challenge)\n* Fold change from V1 (baseline) to C-1 (pre-challenge) in serum anti-S. sonnei LPS IgG titer"}]}, "oversightModule"=>{"isUsExport"=>false, "oversightHasDmc"=>false, "isFdaRegulatedDrug"=>true, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"conditions"=>["Shigellosis"]}, "referencesModule"=>{"references"=>[{"pmid"=>"33813141", "type"=>"BACKGROUND", "citation"=>"Clarkson KA, Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer A, Porter CK, Chakraborty S, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts HP, Feijoo B, Halpern J, Sack D, Riddle MS, Fonck VG, Kaminski RW. Immune response characterization in a human challenge study with a Shigella flexneri 2a bioconjugate vaccine. EBioMedicine. 2021 Apr;66:103308. doi: 10.1016/j.ebiom.2021.103308. Epub 2021 Apr 1."}, {"pmid"=>"9111538", "type"=>"BACKGROUND", "citation"=>"Cohen D, Ashkenazi S, Green MS, Gdalevich M, Robin G, Slepon R, Yavzori M, Orr N, Block C, Ashkenazi I, Shemer J, Taylor DN, Hale TL, Sadoff JC, Pavliakova D, Schneerson R, Robbins JB. Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults. Lancet. 1997 Jan 18;349(9046):155-9. doi: 10.1016/S0140-6736(96)06255-1."}, {"pmid"=>"8926071", "type"=>"BACKGROUND", "citation"=>"Cohen D, Ashkenazi S, Green M, Lerman Y, Slepon R, Robin G, Orr N, Taylor DN, Sadoff JC, Chu C, Shiloach J, Schneerson R, Robbins JB. Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers. Infect Immun. 1996 Oct;64(10):4074-7. doi: 10.1128/iai.64.10.4074-4077.1996."}, {"pmid"=>"32968005", "type"=>"BACKGROUND", "citation"=>"Frenck RW Jr, Dickey M, Suvarnapunya AE, Chandrasekaran L, Kaminski RW, Clarkson KA, McNeal M, Lynen A, Parker S, Hoeper A, Mani S, Fix A, Maier N, Venkatesan MM, Porter CK. Establishment of a Controlled Human Infection Model with a Lyophilized Strain of Shigella sonnei 53G. mSphere. 2020 Sep 23;5(5):e00416-20. doi: 10.1128/mSphere.00416-20."}, {"pmid"=>"37827969", "type"=>"BACKGROUND", "citation"=>"Hausdorff WP, Anderson JD 4th, Bagamian KH, Bourgeois AL, Mills M, Sawe F, Scheele S, Talaat K, Giersing BK. Vaccine value profile for Shigella. Vaccine. 2023 Nov 3;41 Suppl 2:S76-S94. doi: 10.1016/j.vaccine.2022.12.037. Epub 2023 Oct 10."}, {"pmid"=>"29254859", "type"=>"BACKGROUND", "citation"=>"Kotloff KL, Riddle MS, Platts-Mills JA, Pavlinac P, Zaidi AKM. Shigellosis. Lancet. 2018 Feb 24;391(10122):801-812. doi: 10.1016/S0140-6736(17)33296-8. Epub 2017 Dec 16."}, {"pmid"=>"31816066", "type"=>"BACKGROUND", "citation"=>"MacLennan CA, Aguilar AO, Steele AD. Consensus Report on Shigella Controlled Human Infection Model: Introduction and Overview. Clin Infect Dis. 2019 Dec 9;69(Suppl 8):S577-S579. doi: 10.1093/cid/ciz886."}, {"pmid"=>"36146457", "type"=>"BACKGROUND", "citation"=>"MacLennan CA, Grow S, Ma LF, Steele AD. The Shigella Vaccines Pipeline. Vaccines (Basel). 2022 Aug 24;10(9):1376. doi: 10.3390/vaccines10091376."}, {"pmid"=>"35214671", "type"=>"BACKGROUND", "citation"=>"Martin P, Alaimo C. The Ongoing Journey of a Shigella Bioconjugate Vaccine. Vaccines (Basel). 2022 Jan 29;10(2):212. doi: 10.3390/vaccines10020212."}, {"pmid"=>"20056180", "type"=>"BACKGROUND", "citation"=>"Passwell JH, Ashkenazi S, Banet-Levi Y, Ramon-Saraf R, Farzam N, Lerner-Geva L, Even-Nir H, Yerushalmi B, Chu C, Shiloach J, Robbins JB, Schneerson R; Israeli Shigella Study Group. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children. Vaccine. 2010 Mar 2;28(10):2231-2235. doi: 10.1016/j.vaccine.2009.12.050. Epub 2010 Jan 5. Erratum In: Vaccine. 2019 Aug 23;37(36):5504. doi: 10.1016/j.vaccine.2019.07.065."}, {"pmid"=>"22906296", "type"=>"BACKGROUND", "citation"=>"Porter CK, Thura N, Ranallo RT, Riddle MS. The Shigella human challenge model. Epidemiol Infect. 2013 Feb;141(2):223-32. doi: 10.1017/S0950268812001677. Epub 2012 Aug 21."}, {"pmid"=>"29590182", "type"=>"BACKGROUND", "citation"=>"Porter CK, Lynen A, Riddle MS, Talaat K, Sack D, Gutierrez RL, McKenzie R, DeNearing B, Feijoo B, Kaminski RW, Taylor DN, Kirkpatrick BD, Bourgeois AL. Clinical endpoints in the controlled human challenge model for Shigella: A call for standardization and the development of a disease severity score. PLoS One. 2018 Mar 28;13(3):e0194325. doi: 10.1371/journal.pone.0194325. eCollection 2018."}, {"pmid"=>"27581434", "type"=>"BACKGROUND", "citation"=>"Riddle MS, Kaminski RW, Di Paolo C, Porter CK, Gutierrez RL, Clarkson KA, Weerts HE, Duplessis C, Castellano A, Alaimo C, Paolino K, Gormley R, Gambillara Fonck V. Safety and Immunogenicity of a Candidate Bioconjugate Vaccine against Shigella flexneri 2a Administered to Healthy Adults: a Single-Blind, Randomized Phase I Study. Clin Vaccine Immunol. 2016 Dec 5;23(12):908-917. doi: 10.1128/CVI.00224-16. Print 2016 Dec."}, {"pmid"=>"33862589", "type"=>"BACKGROUND", "citation"=>"Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer AM, Kaminski RW, Porter CK, Chakraborty S, Clarkson KA, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts H, Feijoo BL, Halpern J, Sack D, Riddle MS, Fonck VG. Human challenge study with a Shigella bioconjugate vaccine: Analyses of clinical efficacy and correlate of protection. EBioMedicine. 2021 Apr;66:103310. doi: 10.1016/j.ebiom.2021.103310. Epub 2021 Apr 13."}]}, "descriptionModule"=>{"briefSummary"=>"In this challenge study, the bioconjugate candidate vaccine Shigella4V2 will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella sonnei strain compared to participants receiving placebo.", "detailedDescription"=>"The tetravalent Shigella4V2 bioconjugate vaccine candidate will be tested for safety and preliminary efficacy in a Phase 2b controlled human infection model (CHIM) study at three sites in the United States. This trial will be conducted as a parallel-group, randomized, double-blind, multicenter, placebo-controlled study to evaluate the safety, immunogenicity, and efficacy of one dose of Shigella4V2 in healthy Shigella naïve participants 18-50 years of age, administered one month before challenge with S. sonnei 53G strain. It will have two steps:\n\n1. Step 1, a dose selection step, in which participants will receive either one of two doses of Shigella4V2 (high dose or low dose, adjuvanted with Alhydrogel) or placebo (phosphate-buffered saline) at a ratio of 2:2:1, to find the optimal immunogenic dose for Step 2; and\n2. Step 2, in which participants will be randomized to either the Shigella4V2 dose selected in Step 1 or to placebo at a ratio of 1:1. One month after injection, they will be challenged with 1500 CFU of the virulent Shigella sonnei strain 53G. In order to assess the ability of Shigella4V2 to protect against infection with this strain, the attack rate of shigellosis in the group vaccinated with Shigella4V2 will be compared to the group of the participants who received placebo injections."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT"], "maximumAge"=>"50 years", "minimumAge"=>"18 years", "healthyVolunteers"=>true, "eligibilityCriteria"=>"Inclusion Criteria:\n\nStep 1 \\& Step 2:\n\n1. Age 18-50 years (inclusive).\n2. In good health and stable medical condition, determined by MH, laboratory results, and physical examination during screening period.\n3. Negative pregnancy test at the time of injection, for participants of childbearing potential.\n4. Persons of childbearing potential must agree to avoid pregnancy by use of effective contraception for 30 days prior to injection and throughout the study. Participants assigned female at birth and unable to bear children must have this documented (e.g., tubal ligation or hysterectomy).\n5. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.\n6. Availability for the study duration, including all planned follow-up visits and phone calls.\n7. Willingness to refrain from participating in other studies of investigational products until completion of the last study contact.\n\n Step 2 only:\n8. Demonstrated comprehension of the protocol procedures, knowledge of Shigella- associated illness, and passing score of 70% or better on a comprehension assessment. Maximum two attempts are allowed.\n\nExclusion Criteria:\n\nStep 1 \\& Step 2:\n\n1. Participants currently pregnant, lactating, or intending to become pregnant during the study period as reported by the participant.\n2. Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.\n3. Clinically significant abnormalities in vital signs or in screening hematology / blood chemistry as determined by the investigator.\n4. Presence in the serum of HIV 1/2 antibody, HBs-Ag, or HCV antibody (if confirmed positive by Hepatitis C confirmatory test, i.e., recombinant immunoblot assay (RIBA), polymerase chain reaction (PCR)).\n5. Evidence of current excessive alcohol consumption or drug dependence (e.g. according to medical history).\n6. Known or suspected impairment of immunological function (e.g., documented HIV infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder).\n7. BMI \\< 19 or \\> 35 kg/m2.\n8. Recent vaccination or planned vaccination within 14 days of study injection for inactivated vaccines and within 30 days for live vaccines.\n9. Recent receipt of an investigational product within 30 days preceding the study injection or planned during the entire study period.\n10. Recent treatment with immunoglobulins or blood products within 3 months preceding the study injection or planned use during the entire study period.\n11. Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the study injection or planned use during the entire study period.\n12. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world).\n13. Vaccination for or ingestion of Shigella.\n14. Use of systemic antibiotics during the 7 days before injection.\n15. Serum IgG titers to S. sonnei LPS ≥ 2500.\n16. Current occupation involving the handling of Shigella bacteria.\n17. History of allergy to components of the study vaccine (Alhydrogel), to placebo (PBS), or to soy, or any other allergy the investigator deems to increase their risk of AEs in the study.\n18. Any other criteria which, in the investigator's opinion, would compromise the ability of the participant to participate in the study, the safety of the study, or the results of the study.\n19. Part of study personnel or close family member of personnel conducting the study.\n\n Step 2 only:\n20. Personal history of inflammatory ReA.\n21. Positive blood test for HLA-B27 antigen.\n22. Personal history of IBS as defined by Rome IV criteria.\n23. Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day).\n24. Regular use of laxatives, antacids, or other agents to lower stomach acidity.\n25. Known allergy to challenge agent components.\n26. Known allergy to ciprofloxacin or trimethoprim-sulfamethoxazole.\n27. Evidence of IgA deficiency (serum IgA \\< 7 mg/dL or limit of detection of assay).\n28. Planning to travel to Shigella endemic countries before completion of the challenge phase of the study.\n29. Personal history of inflammatory bowel disease."}, "identificationModule"=>{"nctId"=>"NCT06615375", "acronym"=>"S4V03", "briefTitle"=>"A Human Challenge Study to Assess Protection of a Shigella Tetravalent Bioconjugate Vaccine", "organization"=>{"class"=>"INDUSTRY", "fullName"=>"LimmaTech Biologics AG"}, "officialTitle"=>"Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study with the Shigella Tetravalent Bioconjugate Vaccine Shigella4V2", "orgStudyIdInfo"=>{"id"=>"S4V03"}}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"EXPERIMENTAL", "label"=>"Shigella4V2 High dose", "description"=>"1 high dose of Shigella4V2 will be injected intramuscularly in the deltoid muscle", "interventionNames"=>["Biological: Shigella4V2"]}, {"type"=>"EXPERIMENTAL", "label"=>"Shigella4V2 Low dose", "description"=>"1 low dose of Shigella4V2 will be injected intramuscularly in the deltoid muscle", "interventionNames"=>["Biological: Shigella4V2"]}, {"type"=>"PLACEBO_COMPARATOR", "label"=>"Placebo", "description"=>"1 dose of PBS will be injected intramuscularly in the deltoid muscle", "interventionNames"=>["Biological: Placebo"]}], "interventions"=>[{"name"=>"Shigella4V2", "type"=>"BIOLOGICAL", "description"=>"Shigella4V2 is a tetravalent bioconjugate vaccine which consists of the O-antigen polysaccharide of Shigella flexneri 2a, 3a, 6 and of S. sonnei, conjugated to the detoxified Pseudomonas aeruginosa exotoxin A protein as carrier protein.", "armGroupLabels"=>["Shigella4V2 High dose", "Shigella4V2 Low dose"]}, {"name"=>"Placebo", "type"=>"BIOLOGICAL", "description"=>"Phosphate-buffered saline", "armGroupLabels"=>["Placebo"]}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"30030", "city"=>"Atlanta", "state"=>"Georgia", "status"=>"RECRUITING", "country"=>"United States", "contacts"=>[{"name"=>"Michele McCullough", "role"=>"CONTACT", "email"=>"vaccine@emory.edu", "phone"=>"4047121370"}], "facility"=>"Hope Clinic of Emory University", "geoPoint"=>{"lat"=>33.749, "lon"=>-84.38798}}], "centralContacts"=>[{"name"=>"Bettina Wunderlich, PhD", "role"=>"CONTACT", "email"=>"bettina.wunderlich@lmtbio.com", "phone"=>"+41447338555"}], "overallOfficials"=>[{"name"=>"Kawsar R Talaat, MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"Johns Hopkins Bloomberg School of Public Health"}, {"name"=>"Paulina A Rebolledo, MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"Emory University"}, {"name"=>"Robert W Frenck, Jr., MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"Children's Hospital Medical Center, Cincinnati"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"LimmaTech Biologics AG", "class"=>"INDUSTRY"}, "collaborators"=>[{"name"=>"Emory University", "class"=>"OTHER"}, {"name"=>"Johns Hopkins Bloomberg School of Public Health", "class"=>"OTHER"}, {"name"=>"Children's Hospital Medical Center, Cincinnati", "class"=>"OTHER"}], "responsibleParty"=>{"type"=>"SPONSOR"}}}}
