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

NCT01701999 | Completed Phase 2 Results DMC

• 1 other identifier: rBV A/B-CL-001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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.

Conditions

Botulism

Keywords

Botulism Vaccine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Three-Fold Increase in Neutralizing Antibody Concentration (NAC)

  Week 0 to Week 4

• Two-Fold Increase in the Area Under the Neutralizing Antibody Concentration (NAC) Curve

  Week 0 to Week 12

Other Outcomes (1)

• Collected Plasma Volume

  Week 1 to Week 12

Study Arms (1)

Vaccine

EXPERIMENTAL

Biological: rBV A/B

Interventions

rBV A/B BIOLOGICAL

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.

Vaccine

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• California Department of Public Health: lead

Study Sites (2)

California Department of Public Health

Richmond, California, 94804, United States

Location

Battelle Biomedical Research Center

West Jefferson, Ohio, 43162, United States

Location

Related Publications (1)

• 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.

  PMID: 29475762 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Botulism

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neuromuscular Junction Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurotoxicity Syndromes; Foodborne Diseases; Poisoning; Chemically-Induced Disorders

Results Point of Contact

• Title: Dr. Jessica Khouri
• Organization: California Department of Public Health

Jessica.Khouri@cdph.ca.gov

510-231-7600

Study Officials

• Stephen S. Arnon, M.D.

  California Department of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 5, 2012
• Study Start: February 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 16, 2017
• Results First Posted: February 9, 2017

Record last verified: 2017-04

Locations

US (2)