Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid

Study Overview
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Brief Summary
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Study rBV A/B-CL-001 is a Phase 2b, 2-part, open-label, uncontrolled study to evaluate safety, tolerability, and immunogenicity of a single dose of recombinant botulinum vaccine A/B (rBV A/B) for the production of BabyBIG in volunteers previously immunized with the pentavalent botulinum (PBT) toxoid. This study is designed to determine neutralizing antibody levels for botulinum toxin types A and B in healthy subjects who were previously immunized with the PBT for occupational protection and who receive the rBV A/B. Subjects with titers of the neutralizing antibodies against the toxins would be candidates for plasma donation for BabyBIG production.

Official Title
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Phase 2b, Two-part, Open-label, Uncontrolled Study to Evaluate Safety, Tolerability, and Immunogenicity of a Single 40-µg Dose of Recombinant Botulinum Vaccine A/B (rBV A/B) for the Production of BabyBIG® in Volunteers Previously Immunized With Pentavalent Botulinum Toxoid for Occupational Protection

Conditions
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Botulism

Intervention / Treatment
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* Biological: rBV A/B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The volunteer has received pentavalent botulinum toxoid for occupational protection under BB IND 0161, with the previous pentavalent botulinum toxoid dose at least 6 months prior to the planned rBV A/B dose. The volunteer is between the ages of 18 and 69 years at the time of consent. The volunteer is healthy and has an acceptable medical history. The volunteer meets the subject suitability requirements and recommendations for source plasma donors (for Part 2 subjects only). The volunteer, if female and of childbearing potential, is not pregnant or lactating, and agrees to use an acceptable form of FDA-approved contraception for the duration of the study. The volunteer has the ability to understand the requirements of the study and provide informed consent. The volunteer agrees to complete the subject diary on a daily basis for 7 days post-vaccination and to report concomitant medication and adverse events during the study period. The volunteer provides written authorization for use and disclosure of protected health information. The volunteer agrees not to donate blood or blood products (outside of study procedures) during the course of the study. The volunteer has personal health insurance. Exclusion Criteria: Be pregnant or nursing The volunteer has a history of laboratory evidence of syphilis, acquired immunodeficiency syndrome, Creutzfeldt-Jakob disease, or infection with human immunodeficiency viruses 1 or 2, human T cell lymphotropic virus 1, hepatitis B virus, or hepatitis C virus. The volunteer had prior severe local or severe systemic reaction to last immunization with pentavalent botulinum toxoid. The volunteer has a known allergy to aluminum compounds, yeast, or other components of the vaccine. The volunteer has donated one or more units of blood or undergone plasmapheresis within 28 days before screening. The volunteer has received a blood product or immunoglobulin within 6 months of screening or plans to receive such products during the study. The volunteer has received licensed nonliving vaccine within 14 days before study entry or licensed live vaccine within 60 days before study entry. The volunteer has 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. The volunteer has received prescription immunosuppressive or immunomodulatory agents, including parenteral, inhaled, or oral corticosteroids within 3 months before screening or plans on receiving such therapy at any time during the study with the exceptions (Subjects 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). The volunteer has received cytotoxic therapy at any time in the previous 5 years to study entry. The volunteer has an active systemic or recurrent disease that would place the subject at unacceptable risk of injury, require hospitalization, or require surgical intervention. The volunteer has a history of alcohol or drug abuse within 12 months before screening. The volunteer has past, present, or suspected illicit injection drug use. The volunteer has inflammatory, vasculitic, or rheumatic disease, including systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis, or scleroderma. The volunteer has clinically recognized hepatic or renal insufficiency. The volunteer has uncontrolled hypertension. The volunteer has moderate to severe asthma, chronic obstructive pulmonary disease, or other significant pulmonary disease. The volunteer has a seizure disorder. The volunteer has moderate or severe illness or oral temperature of 100.4°F or greater within 3 days prior to immunization. The volunteer is determined by the investigator to be unsuitable for participation in this trial for any reason.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine<br> | Biological: rBV A/B<br>* rBV A/B injections will consist of a single 40 µg injection of total antigen (20 µg of Antigen A and 20 µg of Antigen B) adsorbed to 0.2% (wt/vol) Alhydrogel™, in a total dose volume of 0.5 mL. The vaccine will be administered by intramuscular injection in the deltoid muscle, preferably in the nondominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Four-Fold Increase in Neutralizing Antibody Concentration (NAC) | Proportion of participants achieving a four-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success). | Week 0 to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Three-Fold Increase in Neutralizing Antibody Concentration (NAC) | Proportion of participants achieving a three-fold or greater increase in NAC up to Week 4 compared with Week 0 for both botulinum toxin A and toxin B (a proportion ≥ 0.50 was considered a success) | Week 0 to Week 4 | 
| Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve | Proportion of participants achieving a two-fold increase in the area under the plasma NAC-time curve between Week 0 and Week 12 in comparison with a straight-line extension of the Week 0 NAC to Week 12 for both botulinum toxin A and toxin B. A proportion ≥ 0.50 was considered a success. | Week 0 to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Botulism Vaccine