Investigational Monkeypox Vaccines for Monkeypox

Not currently recruiting at 7 trial locations

Overseen By BioNTech clinical trials patient information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioNTech SE

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Mpox, Smallpox, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates a new RNA-based vaccine, BNT166a, to determine its safety and effectiveness against monkeypox. The study aims to identify the most effective dose while monitoring for side effects. Participants should be generally healthy, unvaccinated for smallpox, and have no history of monkeypox. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that BNT166a, a trial vaccine for monkeypox, has been tested for safety and tolerability. Earlier studies explored different doses to identify a safe and effective option. So far, BNT166a has not shown any major safety issues, and participants have managed the vaccine without serious side effects.

These studies aim to ensure BNT166a is safe and effective in helping the body fight viruses. Although these trials are still in the early stages, the focus on safety involves careful monitoring for any problems. If considering joining a trial, these early results suggest the vaccine is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the investigational monkeypox vaccines, BNT166a and BNT166c, because they offer a novel approach to fighting the virus. Unlike the current standard treatments, which are primarily antiviral medications like Tecovirimat, BNT166a and BNT166c are vaccines that aim to prevent infection altogether. BNT166a, in particular, is being tested at multiple dose levels to optimize its effectiveness and safety. These vaccines could potentially provide a proactive solution by boosting the body's immune response against monkeypox, offering a promising new layer of defense compared to existing treatments that focus on treating symptoms after infection.

What evidence suggests that this trial's vaccine treatments could be effective for monkeypox?

Research has shown that the BNT166a vaccine could effectively protect against monkeypox. In earlier studies, this vaccine completely protected people from various types of the monkeypox virus and prevented severe symptoms like death and skin sores. The vaccine is designed to be effective, safe, and easy to produce. This trial will evaluate different dose levels of BNT166a to determine its effectiveness and safety. These promising results suggest that BNT166a could be a strong tool in preventing monkeypox infections. ^{1 2 3 5 6}

Who Is on the Research Team?

BioNTech Responsible Person

Principal Investigator

BioNTech SE

Are You a Good Fit for This Trial?

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)

Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any trial-specific procedures

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the investigational RNA-based multivalent vaccine candidate BNT166a in a dose-escalation manner

4 weeks

Multiple visits for dosing and monitoring

Follow-up

Participants are monitored for safety, reactogenicity, and immunogenicity after receiving the vaccine

14 months

What Are the Treatments Tested in This Trial?

Interventions

• BNT166a
• BNT166c

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

The BNT162b2 COVID-19 vaccine has a favorable safety profile in adolescents, with over one million participants contributing to the data, showing that most adverse events are mild and include pain at the injection site and fatigue.

Serious adverse events were rare, and while some life-threatening reactions were reported, they occurred infrequently, emphasizing the importance of vaccination in controlling the pandemic and maintaining public confidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of COVID-19 Pfizer-BioNtech (BNT162b2) mRNA vaccination in adolescents aged 12-17 years: A systematic review and meta-analysis. Katoto, PDMC., Brand, AS., Byamungu, LN., et al.[2022]

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]

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 study identified 30 B cell and 19 T cell epitopes in the monkeypox virus's cell surface binding protein, which are crucial for developing a targeted vaccine.

One promising T cell epitope, 'ILFLMSQRY', showed strong binding affinity to the human receptor HLA-B∗15:01, suggesting its potential as a candidate for an epitope-based peptide vaccine against monkeypox.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of B and T Cell Epitopes to Design an Epitope-Based Peptide Vaccine against the Cell Surface Binding Protein of Monkeypox Virus: An Immunoinformatics Study. Mazumder, L., Hasan, MR., Fatema, K., et al.[2023]

A single dose of the JYNNEOS vaccine significantly reduces the incidence of monkeypox, with unvaccinated individuals experiencing 14.3 times more cases than those who received at least one dose.

The JYNNEOS vaccine, approved for preventing both smallpox and monkeypox, is being administered as postexposure prophylaxis, and it is crucial for individuals to complete the full 2-dose series for optimal protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Monkeypox Among Unvaccinated Persons Compared with Persons Receiving ≥1 JYNNEOS Vaccine Dose - 32 U.S. Jurisdictions, July 31-September 3, 2022. Payne, AB., Ray, LC., Kugeler, KJ., et al.[2023]

In a study involving 80 healthcare workers for the BNT162b2 vaccine and 1440 for the AZD1222 vaccine, adverse events (AEs) were reported by 52.5% after the first dose and 76.2% after the second dose of BNT162b2, while 90.9% reported AEs after the first dose of AZD1222, indicating a higher incidence of AEs with the adenovirus-vectored vaccine.

Most AEs were mild to moderate and transient, with no serious incidents like anaphylaxis or neurological AEs reported, suggesting that while AEs are common, they are generally not severe, which could help alleviate vaccine hesitancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Adverse Events between mRNA and Adenovirus-Vectored COVID-19 Vaccines in Healthcare Workers. Wi, YM., Kim, SH., Peck, KR.[2021]

In a study of 57,842 vaccinations with the Pfizer/BioNtech BNT162b2 vaccine, only 0.42% experienced adverse events, primarily related to stress from the immunization process, indicating a high safety profile for the vaccine.

Despite some individuals reporting adverse reactions after their first dose, 90% returned for their second dose, and 87% did not report further reactions, suggesting good vaccine tolerance and completion rates among recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pfizer/BioNtech BNT162b2: adverse events and insights from an Australian mass vaccination clinic for COVID-19. Halder, A., Imamura, H., Condon, S., et al.[2022]

In a study of 273 hospital workers who received two doses of the BNT162b2 vaccine, it was found that anti-RBD antibody levels significantly declined from a median of 9356 AU/mL at 1.5 months to 3952 AU/mL at 3 months after vaccination, indicating a decrease in potential immunity against SARS-CoV-2.

Only 41% of participants maintained anti-RBD antibody levels above the threshold associated with neutralizing activity three months post-vaccination, suggesting that booster doses may be necessary to sustain effective immune protection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decline of antibody titres 3 months after two doses of BNT162b2 in non-immunocompromised adults. Erice, A., Varillas-Delgado, D., Caballero, C.[2022]

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]

Six cases of myocarditis were reported in young males (median age 23) following BNT162b2 vaccination, with five cases occurring after the second dose and one after the first, indicating a potential adverse reaction to the vaccine.

Despite the diagnosis of myocarditis, all patients had a mild clinical course and there was no evidence of COVID-19 infection, suggesting that while myocarditis can occur post-vaccination, it may not be severe in most cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocarditis following COVID-19 mRNA vaccination. Abu Mouch, S., Roguin, A., Hellou, E., et al.[2022]

Citations

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We designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses.

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In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization ...

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pmc.ncbi.nlm.nih.gov/articles/PMC11502315/

Advancements in monkeypox vaccines development

In challenge studies, BNT166a and BNT166c provided full protection, with BNT166a also fully preventing death and lesions in a lethal clade I ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05988203

NCT05988203 | A Clinical Study Investigating the Safety ...

Substudy D is a one group, open-label, Phase IIa substudy to assess the reactogenicity, safety, and immunogenicity of one dose level of BNT166a in ~32 healthy ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0264410X25008953

Review Current and emerging Mpox vaccine strategies

The BNT166 vaccine program, aimed at providing comprehensive protection against monkeypox virus (MPXV), consists of two multivalent mRNA vaccine ...

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Safety and immunogenicity of mpox vaccine candidates

Substudy A will assess the safety and immunogenicity of up to three dose levels of the vaccine candidate BNT166a and one dose level of the vaccine candidate ...