Botulinum Vaccine for Botulism

No longer recruiting at 1 trial location

Overseen By Jessica M Khouri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: California Department of Public Health

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine designed to protect against botulism, a serious illness caused by toxins from the bacteria Clostridium botulinum. Researchers aim to assess the safety and effectiveness of the vaccine, called rBV A/B, in boosting the immune response of healthy individuals who have previously received other botulism vaccines for occupational reasons. The study will also collect blood plasma, which could help treat infants with botulism. Ideal participants are healthy individuals previously vaccinated against botulism toxins for occupational safety. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in botulism prevention.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on prescription immunosuppressive or immunomodulatory agents, you may need to stop them 3 months before enrolling and during the study, unless they are certain types of topical or injectable steroids.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the rBV A/B vaccine is safe and generally well-tolerated. In earlier studies, a single dose of rBV A/B caused no serious side effects. Participants experienced only mild swelling at the injection site, which resolved quickly. Additionally, individuals who had previously received a similar botulinum vaccine encountered no major issues after receiving rBV A/B. This suggests the vaccine is generally safe for those previously vaccinated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the rBV A/B vaccine for botulism because it offers a preventive approach rather than just treating symptoms after exposure. Unlike the standard of care, which typically involves antitoxins administered after symptoms appear, this vaccine is designed to stimulate the body's immune system to fend off botulism toxins before they can cause harm. This proactive strategy could significantly reduce the severity or even prevent the onset of botulism, offering a potentially transformative way to manage this dangerous condition.

What evidence suggests that this vaccine might be an effective treatment for botulism?

Research has shown that the rBV A/B vaccine, which participants in this trial will receive, is safe and helps build immunity in individuals who have already received the pentavalent botulinum toxoid. In earlier studies, a single dose was well-tolerated and effectively triggered an immune response. Although no approved vaccine for botulism exists yet, rBV A/B is being developed to protect against severe botulism poisoning. Preclinical tests revealed no major side effects, except for mild swelling at the injection site. Overall, early data suggest that rBV A/B could be a promising option for preventing botulism. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-69 who have been immunized with pentavalent botulinum toxoid for work safety. They must not be pregnant, agree to birth control, and can't donate blood outside the study until after Week 12. Participants need personal health insurance and should commit to study requirements including a home diary post-vaccination.

Inclusion Criteria

I agree to keep a daily diary for 7 days after vaccination and report any severe side effects.

Participants of childbearing potential must have negative pregnancy test at screening and within 24 hours prior to vaccination, must agree to not become pregnant until after the last plasma donation or until after the Week 12 visit, and must agree to use at least one form of highly effective birth control

Are able to understand the requirements of the study, have provided written informed consent, and have agreed to abide by the study restrictions and return for the required assessments

Exclusion Criteria

I have a history of specific infectious diseases or viruses.

I have taken prescribed immune system altering drugs recently.

I have had chemotherapy in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single 40-µg dose of rBV A/B and undergo plasmapheresis for source plasma collection

12 weeks

Multiple visits for monitoring and plasma collection

Follow-up

Participants are monitored for safety and immunogenicity after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• rBV A/B

Trial Overview The trial tests the safety and immune response of a single dose of rBV A/B in individuals previously vaccinated against botulism for occupational reasons. It's an open-label Phase 2 study without a control group, tracking participants over 12 weeks with a follow-up at six months.

How Is the Trial Designed?

Group I: Vaccine Experimental Treatment 1 Intervention

rBV A/B

Who Is Running the Clinical Trial?

California Department of Public Health

Lead Sponsor

Trials

7

Recruited

5,800+

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X12000503

Preclinical safety assessment of recombinant botulinum ... The rBV A/B vaccine produced no apparent systemic or neurobehavioral toxicity and only transient mild inflammation at the injection site. Together these results ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9196761/

Development and evaluation of a tetravalent botulinum ... The rBV A/B vaccine cannot protect against BoNT/E and BoNT/F, and the PBT vaccine also cannot protect against BoNT/F. Therefore, TBV is an ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01940315

Study Details | NCT01940315 | Phase 3, Randomized, ... The rBV A/B is under development to provide protection of adults 18 to 55 years of age from fatal botulism caused by inhalational intoxication with botulinum ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29475762/

Safety and immunogenicity of investigational recombinant ... A single 0.5 mL dose of rBV A/B was safe, well-tolerated and immunogenic in participants previously immunized with pentavalent botulinum toxoid.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X2501076X

Nontoxic, multi-domain botulinum neurotoxin-LCHC N as ... There are seven BoNT serotypes (A-G) and multiple subtypes. Currently, there is no approved vaccine against botulism available for human use.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22269871/

Preclinical safety assessment of recombinant botulinum ... The rBV A/B vaccine produced no apparent systemic or neurobehavioral toxicity and only transient mild inflammation at the injection site.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X18302160

Safety and immunogenicity of investigational recombinant ... A single 0.5 mL dose of rBV A/B was safe, well-tolerated and immunogenic in participants previously immunized with pentavalent botulinum toxoid.