Ricin
Conditions
Keywords
Ricin, RVEc
Brief summary
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.
Interventions
BIOLOGICALRVEc
Sponsors
US Army Medical Research Institute of Infectious Diseases
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Over Response Rates and Comparisons for ELISA and TNA Titers | Day 7, 14, 28, 35, 42, 56, 63, 70, 84, month 6, 9, and 12 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 RVEc vaccine 20 μg/dose x 3 doses | 10 |
| Group 2 RVEc vaccine 50 μg/dose x 3 doses | 10 |
| Group 3 RVEc vaccine 100 μg/dose x 1 dose | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 35.6 years STANDARD_DEVIATION 8.19 | 35.0 years STANDARD_DEVIATION 7.62 | 32.2 years STANDARD_DEVIATION 8.13 | 34.3 years STANDARD_DEVIATION 7.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 10 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 10 Participants | 9 Participants | 29 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 10 / 10 | 9 / 10 |
| serious Total, serious adverse events | 1 / 10 | 0 / 10 | 1 / 10 |
Outcome results
Primary
Number of Vaccinated Subjects Any Averse Events and by Location and Severity
Time frame: Days 1, 3, 7, 14, and 28 after each vaccination and at 6 and 9 months
Population: Safety population: any subject receiving a vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic severe | 3 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic moderate | 7 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local severe | 1 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic mild | 10 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Any adverse events | 10 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local moderate | 1 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local life-threatening | 0 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local mild | 7 participants |
| Group 1 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic life-threatening | 0 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic life-threatening | 0 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic severe | 2 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Any adverse events | 10 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local mild | 8 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic moderate | 8 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local moderate | 0 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local life-threatening | 0 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic mild | 10 participants |
| Group 2 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local severe | 0 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic mild | 8 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Any adverse events | 9 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local life-threatening | 0 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local severe | 0 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local moderate | 0 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic life-threatening | 2 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic severe | 2 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Systemic moderate | 5 participants |
| Group 3 | Number of Vaccinated Subjects Any Averse Events and by Location and Severity | Local mild | 2 participants |
Secondary
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.
Time frame: Day 7, 14, 28, 35, 42, 56, 63, 70, 84, month 6, 9, and 12
Population: Per-protocol population. Only observations or specimens collected according to the protocol were included in the immunogenicity analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Over Response Rates and Comparisons for ELISA and TNA Titers | ELISA | 10 participants |
| Group 1 | Over Response Rates and Comparisons for ELISA and TNA Titers | TNA | 5 participants |
| Group 2 | Over Response Rates and Comparisons for ELISA and TNA Titers | ELISA | 6 participants |
| Group 2 | Over Response Rates and Comparisons for ELISA and TNA Titers | TNA | 0 participants |
| Group 3 | Over Response Rates and Comparisons for ELISA and TNA Titers | TNA | 1 participants |
| Group 3 | Over Response Rates and Comparisons for ELISA and TNA Titers | ELISA | 6 participants |