First in Human Dose Escalation Study Evaluating the Safety and Immunogenicity of IVT's Shigella-04 Vaccine in Healthy Young Adults

A phase 1 single-site, randomized, double-blind, placebo-controlled, dose-escalation clinical trial to evaluate the safety and immunogenicity of a 2-dose regimen of IM injection of 5 dose formulations of IVT Shigella-04 vaccine with and without adjuvant among 60 healthy individuals aged 18 to 49 years. Approximately 12 eligible participants will be enrolled in the specified 5 sequential dose cohorts and randomized in a 5:1 ratio to receive 2 IM injections of IVT Shigella-04 or placebo (normal saline) at a 28-day interval.

Inclusion criteria

Participants who meet all the following criteria may be included in the study:

• Age 18 to 49 years at the time of Dose 1
• Good general health status, as determined by medical history, physical examination, safety laboratory tests, ECG, vital signs, and clinical judgment
• BMI ≥ 18.0 kg/m2 and ≤ 32.0 kg/m2
• Negative alcohol breath test and urine drug screen results at Screening and on Day 1
• All women: negative serum pregnancy test at Screening and negative urine pregnancy on Day 1
• Women of childbearing potential (see definition in Section 6.6.1): willingness to use a highly effective form of contraception (see list in Section 6.6.1) through 28 days after the last IP dose
• Willingness to attend all protocol visits and to have all protocol-required procedures
• Provision of written informed consent

Exclusion criteria

Participants who meet any of the following criteria will be excluded from the study:

• Currently lactating
• History of shigellosis or participation in a Shigella challenge study
• History of bloody diarrhea without alternative diagnosis
• History of inflammatory bowel disease
• History of anaphylaxis or angioedema
• History of malignancy, excluding nonmelanoma skin cancer, cervical carcinoma in situ, and malignancies considered cured > 5 years prior to Day 1
• History of diabetes mellitus (Individuals with diet-controlled diabetes or history of gestational diabetes are eligible if screening blood glucose is normal and there has been no requirement for antidiabetic medication in the last year.)
• Known hypersensitivity to any of the ingredients in IVT Shigella-04
• Inadequate venous access for repeated phlebotomy
• Any screening laboratory test result outside the normal range and grade ≥ 2 according to the FDA's toxicity grading scale for vaccine trials in healthy adults and adolescents; (Elevated creatine kinase and isolated elevations of bilirubin may be Grade 2 if hepatic transaminases are normal and the Investigator attributes the abnormality to exercise or Gilbert's syndrome. Potential cases of benign ethnic neutropenia should be discussed with the Medical Monitor)
• Positive serologic test for human HIV-1 or HIV-2 antibody, hepatitis B surface antigen, or hepatitis C antibody
• Immunodeficiency or chronic administration (> 14 consecutive days) of immunosuppressant or other immune-modifying drugs (see details in Section 6.6.2), including systemic glucocorticoids, within 6 months before Day 1 (topical, intra-articular, or inhaled glucocorticoids permitted)
• Previous receipt of a licensed or investigational Shigella vaccine
• Planned receipt of any other vaccine through Day 57
• Receipt of blood transfusion or blood product within 6 months before Day 1 or planned receipt through Day 57
• Receipt of any other IP within 90 days before Day 1 or planned receipt through the end of the study
• Planned elective hospitalization or surgical procedure through the end of the study
• Occupational exposure to Shigella (eg, laboratory work)
• Residence ≥ 6 months in a low-income or lower-middle-income country as defined by the World Bank (https://datatopics.worldbank.org/world-development-indicators/the-world-by-income-and-region.html)
• Employee of Inventprise, vendors, or research sites associated with the study
• Any medical, psychiatric, substance use, or social condition that, in the judgment of the Investigator, may pose a risk to the participant or interfere with protocol adherence, assessment of study objectives, or ability to provide informed consent

Temporary Delay Criteria

Administration of IVT Shigella-04/placebo will be delayed for any participant who meets any of the following criteria:

• Receipt of any vaccine in the past 7 days
• Febrile illness (eg, oral temperature ≥ 38.0°C), diarrhea, or other acute illness in the past 48 hours
• Presence of any other sign, symptom, or medication use that could inhibit the proper vaccine administration of IVT Shigella-04/placebo or interpretation of diary data

These criteria are temporary or self-limiting, and IVT Shigella-04/placebo may be administered once the time frame has elapsed/the condition has resolved.