Clinical trial NCT01701999: Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Botulism
Keywords: Botulism Vaccine
Lead sponsor: California Department of Public Health
Sponsor class: OTHER
First posted: 2012-10-05
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Four-Fold Increase in Neutralizing Antibody Concentration (NAC)
timeFrame: Week 0 to Week 4
Secondary outcomes:
measure: Three-Fold Increase in Neutralizing Antibody Concentration (NAC)
timeFrame: Week 0 to Week 4
measure: Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve
timeFrame: Week 0 to Week 12
Other outcomes:
measure: Collected Plasma Volume
timeFrame: Week 1 to Week 12
Locations:
city: Richmond
country: United States
facility: California Department of Public Health
state: California
city: West Jefferson
country: United States
facility: Battelle Biomedical Research Center
state: Ohio
Study officials:
affiliation: California Department of Public Health
name: Stephen S. Arnon, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khouri JM, Motter RN, Arnon SS. Safety and immunogenicity of investigational recombinant botulinum vaccine, rBV A/B, in volunteers with pre-existing botulinum toxoid immunity. Vaccine. 2018 Apr 5;36(15):2041-2048. doi: 10.1016/j.vaccine.2018.02.042. Epub 2018 Feb 21.