Clinical trial NCT02797236: SF2a-TT15 Conjugate Vaccine in Healthy Adult Volunteers
Official title: A Phase I Dose Escalation Study to Assess the Safety and Immunogenicity of the SF2a-TT15 Conjugate Vaccine Against S. Flexneri 2a in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Shigellosis
Bacillary Dysentery
Keywords: Phase I
conjugate vaccine
Shigella flexneri 2a
safety
Immunogenicity
Healthy adults
Lead sponsor: Institut Pasteur
Sponsor class: INDUSTRY
First posted: 2016-06-13
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a first-in-human, single-center, single-blinded, observer-masked randomized, dose escalation (two doses), placebo-controlled study in healthy volunteers.

Detailed description: Subjects will be assigned to one of two cohorts.

1. Cohort 1 will receive the lower dose of 2 μg vaccine (with or without alum adjuvant) or matching placebo.
2. Cohort 2 will receive the higher dose of 10 μg vaccine (with or without alum adjuvant) or matching placebo.

Eligible subjects will be randomized to receive the 2 μg dose or 10 µg without or with alum or matching placebo, at a ratio of 3:1, as three single IM injections. There will be an interval of 28(±3) days) between each treatment.

The study will be conducted in a stepwise approach in which a "Pioneer" Group of 2 subjects (one receiving the active vaccine and one receiving the matching placebo) will receive the first injection. These subjects will remain in-house for a 24-hours medical observation after the first injection (not required in the subsequent injections) Once it has been established that there are no safety concerns in the non-adjuvanted "Pioneer" Groups (and after no less than 48 hrs), the next "Pioneer" group (one subject receiving adjuvanted 2 μg vaccine and one receiving the matching alum placebo) will be injected.

If no safety concerns are raised in this group also, after no less than 48 hrs, the rest of the subjects may receive the first injection.

Eligibility criteria: Inclusion criteria

* Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
* Negative human leukocyte antigen (HLA) -B27 and no history of reactive arthritis
* Negative HIV, Hepatitis B and Hepatitis C serology tests.
* Blood levels of Shigella flexneri 2a LPS IgG antibodies ≤ percentile 80
* No known history of alcohol abuse

Exclusion criteria

* Subjects with a history of clinically significant gastrointestinal disorders or with any history of frequent diarrhea, nausea or emesis, regardless of etiology.
* Individuals with immunosuppressive diseases or under immunosuppressive therapy
* History of culture-proven S. flexneri.
* Individuals who have household contact with/and /or intimate exposure to an individual with laboratory confirmed S. flexneri.
* Having travelled in countries/areas highly endemic for S. flexneri within 3 months prior to enrolment.
* Previous participation in any study in which a Shigella-vaccine candidate was administered.
* Known contraindication, hypersensitivity and/or allergy to the investigational product or its excipients.
* Known hypersensitivity and/or allergy to any drug or vaccine
* Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study.

Primary outcomes:
measure: Adverse Event
timeFrame: 12 months
Secondary outcomes:
measure: Immunogenicity - humoral Immune response
timeFrame: 12 months
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Tel Aviv Souraski Medical Center
Study officials:
References:
citation: Cohen D, Atsmon J, Artaud C, Meron-Sudai S, Gougeon ML, Bialik A, Goren S, Asato V, Ariel-Cohen O, Reizis A, Dorman A, Hoitink CWG, Westdijk J, Ashkenazi S, Sansonetti P, Mulard LA, Phalipon A. Safety and immunogenicity of a synthetic carbohydrate conjugate vaccine against Shigella flexneri 2a in healthy adult volunteers: a phase 1, dose-escalating, single-blind, randomised, placebo-controlled study. Lancet Infect Dis. 2021 Apr;21(4):546-558. doi: 10.1016/S1473-3099(20)30488-6. Epub 2020 Nov 10.