A Human Challenge Study to Assess Protection of a Shigella Tetravalent Bioconjugate Vaccine
NCT ID: NCT06615375
Last Updated: 2025-07-11
Study Results
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Basic Information
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RECRUITING
PHASE2
120 participants
INTERVENTIONAL
2024-11-12
2026-07-31
Brief Summary
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Detailed Description
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1. Step 1, a dose confirmation step, in which a first injection of Shigella4V2 (high dose or low dose, adjuvanted with Alhydrogel) will be administered alongside a placebo arm (phosphate-buffered saline) at a ratio of 2:2:1. A second injection of either Shigella4V2 low dose or placebo will be administered about 6 months after the first injection.
2. Step 2, in which participants will be randomized to the Shigella4V2 dose selected after Step 1 or to placebo at a ratio of 1:1. Participants will receive two injections, 28 days apart. One month after the second injection, they will be challenged with 1500 CFU of the virulent Shigella sonnei strain 53G.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
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Shigella4V2 High dose
1 injection of high dose Shigella4V2 and 1 injection of low dose Shigella4V2 will be injected intramuscularly in the deltoid muscle
Shigella4V2
Shigella4V2 is a tetravalent bioconjugate vaccine
Shigella4V2 Low dose
2 injections of low dose of Shigella4V2 will be injected intramuscularly in the deltoid muscle
Shigella4V2
Shigella4V2 is a tetravalent bioconjugate vaccine
Placebo
2 injections of PBS will be injected intramuscularly in the deltoid muscle
Placebo
Phosphate-buffered saline
Interventions
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Shigella4V2
Shigella4V2 is a tetravalent bioconjugate vaccine
Placebo
Phosphate-buffered saline
Eligibility Criteria
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Inclusion Criteria
1. Age 18-50 years (inclusive).
2. In good health and stable medical condition, determined by MH, laboratory results, and physical examination during screening period.
3. Negative pregnancy test at the time of 1st injection, for participants of childbearing potential.
4. Persons of childbearing potential must agree to avoid pregnancy by use of effective contraception for 30 days prior to 1st 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).
5. Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
6. Availability for the study duration, including all planned follow-up visits and phone calls.
7. Willingness to refrain from participating in other studies of investigational products until completion of the last study contact.
Step 2 only:
8. 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.
Exclusion Criteria
1. Participants currently pregnant, lactating, or intending to become pregnant during the study period as reported by the participant.
2. Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
3. Clinically significant abnormalities in vital signs or in screening hematology / blood chemistry as determined by the investigator.
4. 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)).
5. Evidence of current excessive alcohol consumption or drug dependence (e.g. according to medical history).
6. Known or suspected impairment of immunological function (e.g., documented HIV infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder).
7. BMI \< 19 or \> 35 kg/m2.
8. Recent vaccination or planned vaccination within 14 days of 1st study injection for inactivated vaccines and within 30 days for live vaccines.
9. Recent receipt of an investigational product within 30 days preceding the 1st study injection or planned during the entire study period.
10. Recent treatment with immunoglobulins or blood products within 3 months preceding the 1st study injection or planned use during the entire study period.
11. Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the 1st study injection or planned use during the entire study period.
12. Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world).
13. Vaccination for or ingestion of Shigella.
14. Use of systemic antibiotics during the 7 days before 1st injection.
15. Serum IgG titers to S. sonnei LPS ≥ 2500.
16. Current occupation involving the handling of Shigella bacteria.
17. 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.
18. 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.
19. Part of study personnel or close family member of personnel conducting the study.
Step 2 only:
20. Personal history of inflammatory ReA.
21. Positive blood test for HLA-B27 antigen.
22. Personal history of IBS as defined by Rome IV criteria.
23. Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day).
24. Regular use of laxatives, antacids, or other agents to lower stomach acidity.
25. Known allergy to challenge agent components.
26. Known allergy to ciprofloxacin or trimethoprim-sulfamethoxazole.
27. Evidence of IgA deficiency (serum IgA \< 7 mg/dL or limit of detection of assay).
28. Planning to travel to Shigella endemic countries before completion of the challenge phase of the study.
29. Personal history of inflammatory bowel disease.
18 Years
50 Years
ALL
Yes
Sponsors
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Emory University
OTHER
Johns Hopkins Bloomberg School of Public Health
OTHER
Children's Hospital Medical Center, Cincinnati
OTHER
LimmaTech Biologics AG
INDUSTRY
Responsible Party
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Principal Investigators
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Kawsar R Talaat, MD
Role: PRINCIPAL_INVESTIGATOR
Johns Hopkins Bloomberg School of Public Health
Paulina A Rebolledo, MD
Role: PRINCIPAL_INVESTIGATOR
Emory University
Robert W Frenck, Jr., MD
Role: PRINCIPAL_INVESTIGATOR
Children's Hospital Medical Center, Cincinnati
Locations
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Hope Clinic of Emory University
Atlanta, Georgia, United States
Johns Hopkins Center for Immunization Research
Baltimore, Maryland, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Countries
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Central Contacts
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Facility Contacts
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Bridgett Finley
Role: primary
Tena Pham
Role: primary
References
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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.
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.
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.
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.
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.
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.
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.
MacLennan CA, Grow S, Ma LF, Steele AD. The Shigella Vaccines Pipeline. Vaccines (Basel). 2022 Aug 24;10(9):1376. doi: 10.3390/vaccines10091376.
Martin P, Alaimo C. The Ongoing Journey of a Shigella Bioconjugate Vaccine. Vaccines (Basel). 2022 Jan 29;10(2):212. doi: 10.3390/vaccines10020212.
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.
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.
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.
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.
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.
Other Identifiers
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S4V03
Identifier Type: -
Identifier Source: org_study_id
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