A Human Challenge Study to Assess Protection of a Shigella Tetravalent Bioconjugate Vaccine

NCT06615375 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: S4V03
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Shigellosis

Outcome Measures

Primary Outcomes (1)

• To demonstrate that the Shigella4V2 bioconjugate vaccine protects against shigellosis following challenge with the wild type S. sonnei 53G strain.

  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: 1. Severe diarrhea; OR 2. Moderate diarrhea AND \[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\]; OR 3. Dysentery AND \[fever OR ≥ 1 at least moderate constitutional/enteric symptoms OR ≥ 2 episodes of vomiting in 24 h\]

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccinees vs. placebo

Secondary Outcomes (35)

• The number of challenged participants with shigellosis post-challenge during the inpatient period that responded to Shigella4V2 vaccine compared to participants who received placebo.

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo

• Efficacy - Number of participants with moderate-to-severe shigellosis

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo

• Efficacy - Number of participants with diarrhea of any severity

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo

• Efficacy - Number of participants with severe diarrhea

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo

• Efficacy - Number of participants with moderate or severe diarrhea

  To be evaluated post-challenge during the inpatient period (Day 56 through Day 65) in vaccine responders vs. placebo as well as vaccinees vs. placebo

Study Arms (3)

Shigella4V2 High dose

EXPERIMENTAL

1 injection of high dose Shigella4V2 and 1 injection of low dose Shigella4V2 will be injected intramuscularly in the deltoid muscle

Biological: Shigella4V2

Shigella4V2 Low dose

EXPERIMENTAL

2 injections of low dose of Shigella4V2 will be injected intramuscularly in the deltoid muscle

Biological: Shigella4V2

Placebo

PLACEBO COMPARATOR

2 injections of PBS will be injected intramuscularly in the deltoid muscle

Biological: Placebo

Interventions

Shigella4V2 BIOLOGICAL

Shigella4V2 is a tetravalent bioconjugate vaccine

Shigella4V2 High dose; Shigella4V2 Low dose

Placebo BIOLOGICAL

Phosphate-buffered saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Step 1 and Step 2:
• Age 18-50 years (inclusive).
• In good health and stable medical condition, determined by MH, laboratory results, and physical examination during screening period.
• Negative pregnancy test at the time of 1st injection, for participants of childbearing potential.
• 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).
• Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
• Availability for the study duration, including all planned follow-up visits and phone calls.
• Willingness to refrain from participating in other studies of investigational products until completion of the last study contact.
• Step 2 only:
• 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.

You may not qualify if:

• Step 1 and Step 2:
• Participants currently pregnant, lactating, or intending to become pregnant during the study period as reported by the participant.
• Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
• Clinically significant abnormalities in vital signs or in screening hematology / blood chemistry as determined by the investigator.
• 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)).
• Evidence of current excessive alcohol consumption or drug dependence (e.g. according to medical history).
• Known or suspected impairment of immunological function (e.g., documented HIV infection, asplenia/splenectomy, or history of autoimmune disease or lymphoproliferative disorder).
• BMI \< 19 or \> 35 kg/m2.
• Recent vaccination or planned vaccination within 14 days of 1st study injection for inactivated vaccines and within 30 days for live vaccines.
• Recent receipt of an investigational product within 30 days preceding the 1st study injection or planned during the entire study period.
• Recent treatment with immunoglobulins or blood products within 3 months preceding the 1st study injection or planned use during the entire study period.
• 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.
• Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world).
• Vaccination for or ingestion of Shigella.
• Use of systemic antibiotics during the 7 days before 1st injection.

Sponsors & Collaborators

• LimmaTech Biologics AG: lead
• Emory University: collaborator
• Johns Hopkins Bloomberg School of Public Health: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (3)

Hope Clinic of Emory University

Atlanta, Georgia, 30030, United States

Location

Johns Hopkins Center for Immunization Research

Baltimore, Maryland, 21205, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (14)

• 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: 33813141 BACKGROUND

• 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.

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• 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.

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• 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: 32968005 BACKGROUND

• 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.

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• 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.

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• 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.

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• 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: 36146457 BACKGROUND

• 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: 35214671 BACKGROUND

• 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.

  PMID: 20056180 BACKGROUND

• 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: 22906296 BACKGROUND

• 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: 29590182 BACKGROUND

• 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: 27581434 BACKGROUND

• 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.

  PMID: 33862589 BACKGROUND

MeSH Terms

Conditions

Dysentery, Bacillary

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Kawsar R Talaat, MD

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

• Paulina A Rebolledo, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Robert W Frenck, Jr., MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: September 26, 2024
• Study Start: November 12, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)