Botulism
Conditions
Brief summary
This Phase 2, open-label, uncontrolled study designed to evaluate safety, tolerability, and immunogenicity of a single dose of rBV A/B in healthy participants previously immunized with pentavalent botulinum toxoid (or pentavalent botulinum toxoid and rBV A/B) for occupational protection will be conducted to collect source plasma for potential use in the production of BabyBIG and to evaluate safety and immunogenicity of the vaccine in these participants over a 12-week period, with a follow-up safety assessment at 6 months.
Interventions
BIOLOGICALrBV A/B
Recombinant Botulinum Vaccine A/B, rBV A/B
Sponsors
California Department of Public Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
Yes
Inclusion criteria
1. Have received pentavalent botulinum toxoid (or pentavalent botulinum toxoid and rBV A/B) for occupational protection under BB IND 0161 (or BB-IND-0161 and IND 015155) 2. Be 18 to 69 years old at the time of consent 3. Be healthy and have an acceptable medical history that will not interfere with the objectives of the study 4. Meet the participant suitability requirements and recommendations for source plasma donors outlined in Appendix A. 5. If female, and of childbearing potential, have a negative pregnancy test at screening and within 24 hours prior to vaccination and must not plan to become pregnant until after the last plasma donation or until the Week 12 visit (\[whichever occurs last\]. 6. Have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an informed consent form (ICF) approved by the Committee for the Protection of Human Subjects, and have agreed to abide by the study restrictions and to return for the required assessments 7. Agree to complete the participant home diary on a daily basis for 7 days post vaccination, as well as to report any adverse events and concomitant medications during the study period 8. Have provided written authorization for use and disclosure of protected health information 9. Agree not to donate blood or blood products (outside of study procedures) until after the last plasma donation or until the Week 12 visit (whichever occurs last) 10. Have personal health insurance
Exclusion criteria
1. Be pregnant or nursing 2. Have a history of laboratory evidence of syphilis, acquired immunodeficiency syndrome, Creutzfeldt-Jakob disease, or infection with human immunodeficiency viruses (HIV) 1 or 2, human T-cell lymphotropic virus 1, hepatitis B virus (HBV), or hepatitis C virus (HCV) 3. Have had a prior severe (Grade 3 or higher) local or severe (Grade 3 or higher) systemic reaction to last immunization with pentavalent botulinum toxoid or a prior severe immediate hypersensitivity reaction or severe systemic reaction to last vaccination on Day 0 with rBV A/B 4. Have known allergy to aluminum, yeast, or other components of the vaccine 5. Have donated one or more units of blood or undergone plasmapheresis within 49 days of the Vaccination Visit (Day 0) 6. Have received blood product or immunoglobulin within 6 months prior to study entry or plans to receive such products during the study period (exclusive of returned red blood cells as part of the plasmapheresis procedure). For participants who choose to donate plasma, this will apply until their last plasma donation or at the Week 12 visit (whichever occurs last) 7. Have received licensed nonliving vaccine within 14 days prior to study entry, or licensed live vaccine within 60 days prior to study entry 8. Have received investigational products (drugs, biologics, vaccines, or implantable devices) 60 days prior to study entry or plans to receive experimental products at any time during the study period. For participants who choose to donate plasma, this will apply until their last plasma donation or at the Week 12 visit (whichever occurs last) 9. Have received prescription immunosuppressive or immunomodulatory agents, including parenteral, inhaled, or oral corticosteroids within 3 months of study entry or plans on receiving such therapy at any time during the study period \[For participants who choose to donate plasma, this will apply until their last plasma donation or at the Week 12 visit (whichever occurs last)\], with the exceptions mentioned below * Participants who have used prescription topical steroids may be enrolled 2 weeks after the therapy is completed * Intra-articular, bursal, or tendon injectable steroids are permitted * Any over-the-counter topical steroid use is permitted * Ophthalmic and intranasal steroids are permitted 10. Have received cytotoxic therapy at any time in the previous 5 years before study entry 11. Have an active systemic or recurrent disease that would place the participant at unacceptable risk of injury, require hospitalization, or require surgical intervention (This includes active mental illness or history of mental illness not responsive to treatment.) 12. Have a history of alcohol or drug abuse or dependence within 12 months of study entry 13. Have past, present, or suspected illicit injection drug use 14. Have inflammatory, vasculitic, or rheumatic disease, including systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis, or scleroderma (Stable osteoarthritis treated with physical therapy and nonsteroidal anti inflammatory drugs is not an exclusion criterion.) 15. Have any acute or chronic neuromuscular or neurologic disorder 16. Have clinically confirmed hepatic or renal insufficiency 17. Have uncontrolled hypertension, as defined a systolic blood pressure greater than 160 mmHg and diastolic blood pressure greater than 90 mmHg 18. Have moderate to severe asthma, chronic obstructive pulmonary disease, or other significant pulmonary disease 19. Have a seizure disorder 20. Have moderate or severe illness or oral temperature of 100.4°F or greater within 3 days of Vaccination Visit (Day 0) 21. Be unsuitable for participation in this study for any reason, as assessed by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC) | Week 0 to Week 4 | Neutralizing Antibody Concentration in Plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving Greater Than 2-Fold Increase in Neutralizing Antibody Concentration (NAC) | Week 0 to 12 | Neutralizing Antibody Concentration in Plasma |
Other
| Measure | Time frame | Description |
|---|---|---|
| Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer | Week 0 to 4 | Neutralizing Antibody Concentration in Plasma |
Countries
United States
Participant flow
Recruitment details
A total of 32 participants were enrolled during the recruiting period from 07 March 2019 to 29 August 2019.
Pre-assignment details
All enrolled participants participated in the study.
Participants by arm
| Arm | Count |
|---|---|
| 0.5 mL rBV A/B A single 0.5-mL intramuscular injection of 40 μg of rBV A/B was administered to each participant on Day 0 to stimulate the production of antibodies against botulinum toxin type A and type B. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Out-of-limit pulse | 2 |
| Overall Study | Red blood cell loss | 1 |
Baseline characteristics
| Characteristic | 0.5 mL rBV A/B |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 46.6 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Previous BabyBIG Plasma Donor | 24 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 28 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 5 / 32 |
| serious Total, serious adverse events | 1 / 32 |
Outcome results
Primary
Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC)
Neutralizing Antibody Concentration in Plasma
Time frame: Week 0 to Week 4
Population: Immunogenicity Population: All participants who received rBV A/B, had a baseline NAC, and had at least one post-vaccination immunogenicity assessment up to and including four weeks after administration of rBV A/B
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC) | Proportion of participants with a ≥4x increase in type A NAC | .844 proportion of participants |
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC) | Proportion of participants with a ≥3x increase in type A NAC | .938 proportion of participants |
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC) | Proportion of participants with a ≥4x increase in type B NAC | .875 proportion of participants |
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 3- or 4-Fold Increases in Neutralizing Antibody Concentration (NAC) | Proportion of participants with a ≥3x increase in type B NAC | .906 proportion of participants |
Comparison: Consider increase from baseline to post-dose values. Parameter is proportion achieving desired increase (≥ 3x or 4x increase in Type A and Type B NAC).95% CI: [0.672, 0.947]
Secondary
Proportion of Subjects Achieving Greater Than 2-Fold Increase in Neutralizing Antibody Concentration (NAC)
Neutralizing Antibody Concentration in Plasma
Time frame: Week 0 to 12
Population: Immunogenicity Population: All participants who received rBV A/B, had a baseline NAC, and had at least one post-vaccination immunogenicity assessment up to and including four weeks after administration of rBV A/B
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 2-Fold Increase in Neutralizing Antibody Concentration (NAC) | two times or greater increase in type A NAC compared with Week 0 | .906 proportion of participants |
| 0.5 mL rBV A/B | Proportion of Subjects Achieving Greater Than 2-Fold Increase in Neutralizing Antibody Concentration (NAC) | two times or greater increase in type B NAC compared with Week 0 | .844 proportion of participants |
Other Pre-specified
Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer
Neutralizing Antibody Concentration in Plasma
Time frame: Week 0 to 4
Population: Plasma-Donating Population: all participants who received rBV A/B and donated at least one plasma unit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 0.5 mL rBV A/B | Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer | Total volume of plasma from all donating participants | 470,102 mL |
| 0.5 mL rBV A/B | Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer | Total volume of plasma from donating participants with any positive titer | 470,102 mL |
| 0.5 mL rBV A/B | Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer | Total volume of plasma from donating participants with positive anti-A titer | 470,102 mL |
| 0.5 mL rBV A/B | Volume of Plasma Collected With an Acceptable Anti-type A or Anti-type B Titer | Total volume of plasma from donating participants with positive anti-B titer | 469,411 mL |