Investigational Monkeypox Vaccines for Monkeypox

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: BioNTech SE

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Mpox, Smallpox, Diabetes, Hypertension, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is a dose-escalation, Phase I/II study evaluating the safety, tolerability, reactogenicity and immunogenicity of the investigational RNA-based multivalent vaccine candidate BNT166a for active immunization against monkeypox (mpox). This study started with substudy A (SSA) and substudy B (SSB) for which recruitment has been completed. A Substudy C (SSC) was planned, but the sponsor decided not to conduct it. This study will therefore continue with substudy D (SSD). In SSA and SSB, dosing started with an initial sentinel group, followed by the expansion cohort. This study was initially planned to investigate two vaccine candidates (the quadrivalent BNT166a and the trivalent BNT166c). The sponsor decided to not activate the groups with BNT166c.

Will I have to stop taking my current medications?

The trial protocol mentions that certain medications are prohibited, but it does not specify which ones. It is best to discuss your current medications with the study team to see if any adjustments are needed.

What data supports the effectiveness of the treatment BNT166a, BNT166a, BNT166c, BNT166c, BNT166c for monkeypox?

Research shows that a similar vaccine, MVA-BN, is effective in reducing the risk of monkeypox infection by 86% after a single dose in high-risk groups. Additionally, another vaccine, LC16m8, has been shown to protect monkeys from monkeypox, suggesting potential effectiveness in humans. ^{1 2 3 4 5}

Research Team

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Eligibility Criteria

This trial is for healthy adults with a BMI between 18.5 and 30 kg/m^2, weighing at least 50 kg, without prior smallpox vaccination (ages 18-45) or with past vaccination before 1980 (ages 50-65). Participants must not have immune deficiencies, uncontrolled diseases, recent vaccinations outside the study, or be pregnant. They should agree to use effective contraception.

Inclusion Criteria

Negative Hepatitis B surface antigen test result and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction (PCR) test result if the anti-HCV is positive at Visit 0

Agree not to enroll in another trial with an IMP starting from Visit 0 and until the end of this trial (Visit 12)

I am between 18 and 45 years old.

Exclusion Criteria

I have been vaccinated against mpox or vaccinia virus.

I have or had type 1 or type 2 diabetes, even if it's diet-controlled.

History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history

Treatment Details

Interventions

• BNT166a (Cancer Vaccine)
• BNT166c (Cancer Vaccine)

Trial Overview The trial tests two RNA-based monkeypox vaccines: BNT166a for those who've never had a smallpox vaccine and BNT166c for those vaccinated before 1980. It's randomized and partially observer-blind to assess safety and immune response starting with low doses that increase over time.

Participant Groups

Group I: SSD - BNT166a Experimental Treatment 1 Intervention

One dose level based on SSA and SSB data

Group II: SSB - BNT166a DL2 Experimental Treatment 1 Intervention

One dose level

Group III: SSA - BNT166a Dose Level (DL)1 Experimental Treatment 1 Intervention

One dose level

Group IV: SSA - BNT166a DL3 Experimental Treatment 1 Intervention

One dose level

Group V: SSA - BNT166a DL2 Experimental Treatment 1 Intervention

One dose level

Who Is Running the Clinical Trial?

BioNTech SE

Lead Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

The study involved 745 participants and demonstrated that the MVA-BN vaccine significantly boosts neutralizing antibody levels after both primary vaccination and a booster, indicating strong immunological memory.

No safety concerns were reported, suggesting that MVA-BN is a safe option for smallpox and monkeypox prevention, with effective long-term immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines. Ilchmann, H., Samy, N., Reichhardt, D., et al.[2023]

The LC16m8 strain of the vaccinia virus vaccine effectively induced protective immunity against monkeypox in nonhuman primates, showing no symptoms after exposure, while nonimmunized controls exhibited typical disease symptoms.

Both LC16m8 and the parental Lister strain provided protection against monkeypox, indicating that LC16m8 could be a valuable vaccine option for preventing both monkeypox and smallpox, especially given its safety profile with only mild side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox. Saijo, M., Ami, Y., Suzaki, Y., et al.[2023]

In a study of 2,054 eligible male individuals, a single subcutaneous dose of the MVA-BN vaccine showed an impressive 86% effectiveness in reducing the risk of monkeypox (mpox) infection after at least 90 days of follow-up.

The study found that only 5 infections occurred in vaccinated individuals compared to 16 in unvaccinated individuals, highlighting the vaccine's significant protective effect in a high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of a single dose of mpox vaccine in males. Wolff Sagy, Y., Zucker, R., Hammerman, A., et al.[2023]

The monkeypox virus shares 90% of its genetic material with the smallpox virus and is transmitted from wild animals to humans, highlighting its zoonotic nature.

The MVA-BN vaccine, classified as non-replicative, is currently used against monkeypox and may help prevent or reduce the severity of the disease during the ongoing 2022 outbreak, especially for close contacts of confirmed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines against monkeypox. Reina, J., Iglesias, C.[2023]

The monkeypox virus shares 90% of its genetic material with the smallpox virus and is transmitted from wild animals to humans, highlighting its zoonotic nature.

The MVA-BN vaccine, classified as non-replicative, is currently recommended for use against monkeypox, especially as pre-exposure prophylaxis for close contacts of confirmed cases, due to its proven efficacy and lower side effects compared to other vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vaccines against monkeypox]. Reina, J., Iglesias, C.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of a single dose of mpox vaccine in males. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

Vaccines against monkeypox. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

[Vaccines against monkeypox]. [2023]