Safety and Immunogenicity Study of Recombinant Ricin Toxin A-Chain Vaccine (RVEc™)

Study Overview
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Brief Summary
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This study is a Phase 1, escalating, multiple-dose, single-center study to evaluate the safety and immunogenicity of the RVEc vaccine. The two principal hypotheses to be tested are: RVEc vaccine will display an acceptable safety profile as determined by adverse event data and RVEc vaccine will elicit ELISA immunoglobulin G (IgG) titers greater than or equal to 1:500 and toxin-neutralizing antibody (TNA) anti-ricin toxin-neutralizing antibody titers greater than or equal to 1:50 in vaccine recipients.

Official Title
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Phase 1 Escalating, Multiple-Dose Study to Evaluate the Safety and Immunogenicity of Recombinant Ricin Toxin A-Chain 1-33/44-198 (rRTA 1-33/44-198) Vaccine (RVEc™) in Healthy Adults

Conditions
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Ricin

Intervention / Treatment
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* Biological: RVEc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study subjects must be 18-50 years old. Subjects must weigh at least 110 pounds. Subjects must be in good health as judged from medical history, physical examination, EKG and chest x-ray, complete blood count (CBC) with differential, clinical chemistries, urinalysis, hepatitis serology, and HIV antibody test, and be medically cleared for participation by an investigator. If any HIV or hepatitis testing is positive, the individual will be provided with counseling and referral for health care. Females of childbearing potential must have a negative pregnancy test on vaccination day before each dose and agree to not become pregnant or breastfeed for 3 months after the last dose of the vaccine and be willing to use a reliable form of contraception during the study. Study subjects must read and sign an approved informed consent. Study subjects must be willing to complete a subject diary card after each vaccination. Study subjects must be willing to return for all follow-up visits. Study subjects must agree to report any adverse event (AE) that may or may not be associated with administration of the investigational product through the 9-month follow-up visit. Study subjects will report all serious adverse events for the duration of the study. Exclusion Criteria: Body weight less than 110 pounds. Acute or chronic medical conditions or immunodeficiency from a medical condition or medical treatment, medications, or dietary supplements that, in the investigator's opinion, would impair the subject's ability to respond to vaccination. Severe hypersensitivity to any vaccine (anaphylaxis, angioedema, bronchospasm, or laryngospasm). History of asthma, chronic obstructive pulmonary disease, or other current/residual disease of the lungs. Clinically significant abnormal laboratory tests. Current smoker. Any known allergies to sodium succinate, Tween-20 (a detergent), aluminum hydroxide, or kanamycin. Previously received ricin toxin vaccine or has antibodies to ricin toxin proteins. Receipt of licensed vaccines within 30 days prior to the start of the study or plans to receive other vaccines during the initial 9 months of the study (the only exceptions are the inactivated influenza vaccine that can be received at least 30 days after RVEc Dose 3). Receipt of investigational drug/test product within 30 days prior to entry or within the initial 9 months of the study. Females: Pregnant or breastfeeding. Enrolled in another greater than minimal risk study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>RVEc vaccine 20 μg/dose x 3 doses | Biological: RVEc<br> <br> * Other names: Recombinant Ricin Toxin A-Chain 1-33/44-198 (rRTA 1-33/44-198) Vaccine;|
| Experimental: Group 2<br>RVEc vaccine 50 μg/dose x 3 doses | Biological: RVEc<br> <br> * Other names: Recombinant Ricin Toxin A-Chain 1-33/44-198 (rRTA 1-33/44-198) Vaccine;|
| Experimental: Group 3<br>RVEc vaccine 100 μg/dose x 1 dose | Biological: RVEc<br> <br> * Other names: Recombinant Ricin Toxin A-Chain 1-33/44-198 (rRTA 1-33/44-198) Vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Vaccinated Subjects Any Averse Events and by Location and Severity |  | Days 1, 3, 7, 14, and 28 after each vaccination and at 6 and 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Over Response Rates and Comparisons for ELISA and TNA Titers | Overall response is defined as a subject having a response at any time after vaccination. A response is defined as subjects who developed total ELISA IgG titers (≥ 1:500) and TNA anti-ricin toxin-neutralizing antibody titers (≥ 1:50) at each scheduled time point for which blood samples were taken for each group and over the entire study period to study completion. | Day 7, 14, 28, 35, 42, 56, 63, 70, 84, month 6, 9, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ricin, RVEc