Ricin Poisoning
Conditions
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of a single 50-μg booster dose of RVEc. Subjects will be recruited from the cohort that received three 50-μg doses of RVEc in a Phase 1 trial (NCT01317667).
Interventions
BIOLOGICAL50-μg booster dose RVEc
Subjects will be recruited from the 10 subjects who received three 50-μg doses of RVEc during the Phase 1 trial. Subjects will receive a single booster dose only and will be followed for 6 months after vaccination.
Sponsors
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Study subjects must have received the 3 priming doses of RVEc at the 50-µg dosage. * Study subjects must be 18 years old at time of screening and no older than 50 years old at time of vaccination. * Subjects must weigh at least 110 pounds at time of screening. * Subjects must be in good health as judged from medical history, physical examination, EKG, hematology, clinical chemistries, urinalysis, hepatitis serology, and HIV antibody test (Table 4) 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 child-bearing potential must have a negative pregnancy test on screening and the morning of vaccination prior to receipt of the vaccine and must agree to use a highly effective method of birth control during the first 3 months following receipt of RVEc. A highly effective method of birth control is defined as one with a failure rate of less than 1% per year. Acceptable birth control methods that meet this criterion include hormonal implants and injectables (Norplant, Depo-Provera, Lunelle, and Etonogestrel), combined oral contraceptives, the intrauterine devices (IUDs) Copper T (380-A) or Mirena (Levonorgestrel Intrauterine System), female sterilization (tubal ligation), sexual abstinence, or a vasectomized partner. * Female subjects must also agree not to breastfeed until at least 3 months after receiving the RVEc. * Study subjects must read and sign an approved informed consent. * Study subjects must be willing to return for all follow-up visits. * Study subjects must agree to report any AE that may or may not be associated with administration of the investigational product through the 6-month follow-up/closeout visit. * Study subjects must agree to abstain from excessive exercise (more than the usual routine) and excessive alcohol consumption (exceeds more than 2 drinks for males or 1 drink for females daily or binge drinking) for the duration of study participation.
Exclusion criteria
* 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. Use of corticosteroids, other than inhaled corticosteroids, will not be permitted. * Severe hypersensitivity to any vaccine (anaphylaxis, angioedema, bronchospasm, or laryngospasm). * History of asthma, chronic obstructive pulmonary disease, or other current/residual diseases of the lungs. * Clinically significant abnormal laboratory tests. * Current smoker. * Any known allergies to sodium succinate, Tween-20 (a detergent), aluminum hydroxide, or kanamycin. * Receipt of any vaccine or investigational product within 30 days before or after vaccination with RVEc. * Receipt of RVEc is contraindicated based on SIRVA checklist/screening, as determined by PI.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Six months |
Secondary
| Measure | Time frame |
|---|---|
| Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Six months |
| Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Six months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50-μg Booster Dose RVEc Subjects will be receive one 50-μg dose of RVEc
50-μg booster dose RVEc: Subjects will be recruited from the 10 subjects who received three 50-μg doses of RVEc during the Phase 1 trial. Subjects will receive a single booster dose only and will be followed for 6 months after vaccination. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | 50-μg Booster Dose RVEc |
|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 10.03 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity.
Time frame: Six months
Population: All statistical analysis of safety data was conducted using 4 subjects at every time point except Day 180 (for which there were 3 subjects).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated without symptoms | 0 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated with any severity of local reaction | 3 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated with mild systemic reactions | 3 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated with moderate systemic reactions | 2 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated with severe systemic reactions | 1 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated with life-threating systemic reaction | 0 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated that developed hypernatraemia | 3 participants |
| 50-μg Booster Dose RVEc | Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity. | Vaccinated that developed injection site pain | 3 participants |
Secondary
Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50)
Time frame: Six months
Population: All statistical analysis of immunogenicity data was conducted using 4 subjects at every time point except Day 84 and 180 (for which there were 3 subjects).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 0 | 0 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 1 | 0 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 3 | 0 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 7 | 3 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 14 | 4 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 28 | 4 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 42 | 4 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 56 | 4 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 84 | 3 participants |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed TNA Anti-ricin Toxin-neutralizing Antibody Titers (≥ 1:50) | Day 180 | 3 participants |
Secondary
Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500)
Time frame: Six months
Population: All statistical analysis of immunogenicity data was conducted using 4 subjects at every time point except Day 84 and 180 (for which there were 3 subjects).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 0 | 0 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 1 | 1 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 3 | 1 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 7 | 3 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 14 | 4 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 28 | 4 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 42 | 4 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 56 | 4 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 84 | 3 Subjects with Total ELISA IgG (≥ 1:500) |
| 50-μg Booster Dose RVEc | Number of Subjects Who Developed Total ELISA IgG Titers (≥ 1:500) | Day 180 | 3 Subjects with Total ELISA IgG (≥ 1:500) |