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

Official title

First-in-human, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study Evaluating the Safety and Immunogenicity of IVT Shigella-04 in Healthy Young Adults

Overview

Phase 1 trial to evaluate the Safety and Immunogenicity of Inventprise's (IVT) Shigella-04 in Healthy Young Adults

Detailed description

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.

Interventions

• Biological IVT Shigella-04
  Preventative vaccine for Shigella protection against 4 unique serotypes
• Biological Placebo (0.9% saline)
  Subjects dosed with 0.9% saline

Primary outcome measures

• Percentage of participants with reactogenicity events for 7 days after each dose [Time frame: 7 days after Doses 1 and 2]
• Percentage of participants with adverse events (AEs) from Dose 1 to 28 days after Dose 2 [Time frame: After Dose 1 to 6 months after Dose 2]
• Percentage of participants with medically attended AE's (MAAEs) from Dose 1 to 6 months after Dose 2 [Time frame: After Dose 1 to 6 months after Dose 2]
• Percentage of participants with newly diagnosed chronic medical conditions (NDCMCs) from Dose 1 to 6 months after Dose 2 [Time frame: After Dose 1 to 6 months after Dose 2]
• Percentage of participants with AEs of special interest (AESIs) from Dose 1 to 6 months after Dose 2 [Time frame: After Dose 1 to 6 months after Dose 2]
• Percentage of participants with serious AEs (SAEs) from Dose 1 to 6 months after Dose 2 [Time frame: After Dose 1 to 6 months after Dose 2]

Secondary outcome measures (6)

• Percentage of participants achieving 4-fold increase in anti-IpaB and serotype-specific anti-OPS immunoglobulin G (IgG) concentration at 28 days after each dose and 6 months after Dose 2 [Time frame: At 28 days after each dose and 6 months after Dose 2]
• Geometric mean concentration (GMCs) of anti-IpaB and serotype-specific anti-OPS IgG at 28 days after each dose and 6 months after Dose 2 [Time frame: At 28 days after each dose and 6 months after Dose 2]
• Geometric mean fold rises (GMFRs) in anti-IpaB and serotype-specific anti-OPS IgG concentration at 28 days after each dose and 6 months after Dose 2 [Time frame: At 28 days after each dose and 6 months after Dose 2]
• Percentage of participants achieving 4-fold increase in serotype-specific anti-OPS functional antibody titer measured by serum bactericidal assay (SBA) at 28 days after each dose [Time frame: At 28 days after each dose]
• Geometric mean titers (GMTs) of serotype-specific anti-OPS functional antibody as measured by SBA at 28 days after each dose [Time frame: At 28 days after each dose]
• GMFRs in serotype-specific anti-OPS functional antibody titer as measured by SBA at 28 days after each dose [Time frame: At 28 days after each dose]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Medpace Clinical Pharmacology Unit — Cincinnati

Identifiers

NCT: NCT07205926 · IVT 514

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗