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TuberculosisPhase 1NCT05537038

Safety and Immune Responses After Vaccination With Two Investigational RNA-based Vaccines Against Tuberculosis in Healthy Volunteers

A Phase 1 study testing BNT164a1 and BNT164b1 in people with Tuberculosis, run by BioNTech SE at 3 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized, placebo-controlled, double-blind, safety and dose-finding Phase Ia trial will evaluate four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Tuberculosis
What is being tested?
BNT164a1 and BNT164b1
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
3 sitesGermany
Study dates
18 Apr 2023to 8 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Have given informed consent by signing and dating an informed consent form (ICF) before initiation of any trial-specific procedures.
  • Are 18 to 55 years of age inclusive and have a body mass index (BMI) over 18.5 kg/m^2 and under 35 kg/m^2 and weigh at least 50 kg.
  • Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions, and other requirements of the trial. This includes that they are able to understand and follow trial-related instructions.
  • Are overall healthy in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram [ECG]), and be interferon gamma release assay (IGRA)-negative for tuberculosis.
  • Hemoglobin ≥12.0 g/dL for volunteers who were born female, ≥13.0 g/dL for volunteers who were born male.
  • Volunteers of childbearing potential (VOCBP) that have a negative serum beta-human chorionic gonadotropin pregnancy test result at Visit 0 and negative urine pregnancy test results before each Investigational medicinal product (IMP) injection. Volunteers born female that are postmenopausal (confirmed by follicle stimulating hormone [FSH]) or permanently sterilized (verified by medical records) will not be considered VOCBP.
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  • VOCBP who agree to practice a highly effective form of contraception and to require their male partners to use condoms, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this trial.
  • VOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this trial.
  • Men who are sexually active with a partner of childbearing potential and have not had a vasectomy who agree to use condoms and to practice a highly effective form of contraception during the trial, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this trial.
  • Men who are willing to refrain from sperm donation, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this trial.
  • Negative alcohol breath test at Visit 0 or Visit 1.
  • With no current use and no history of drug abuse (for amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, tricyclic antidepressants) that in the opinion of the investigator may jeopardize participants' participation and integrity of the trial results.

Who cannot join

  • Any existing condition which may affect vaccine injection and/or assessment of local reactions assessment at the injection site, e.g., tattoos, severe scars, etc.
  • Any bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
  • History of prior tuberculosis vaccination (Bacillus Calmette-Guérin), Mycobacterium tuberculosis infection, treatment for tuberculosis, or history of mycobacterial disease including non-tuberculous mycobacterial infections.
  • Current febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours prior to Dose 1 in this trial (if presented at Visit 0, temporary deferral is allowed).
  • History of cardiovascular diseases (diagnosed within the last 3 years), e.g., myocardial infarction, congestive heart failure, cardiomyopathy, clinically significant arrhythmias, myocarditis, or pericarditis.
  • History of syncope (fainting) in association with administration of injectable vaccines.
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  • Known or suspected immunodeficiency.
  • History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMP.
  • Positive test result at Visit 0 or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  • Any planned non-trial vaccinations within 28 days before Dose 1 and continuously until 28 days after Dose 3 (Visit 9).
  • Note: Licensed vaccines (including inactivated, mRNA, and live attenuated vaccines) are allowed to be given at least 28 days before or 28 days after each IMP injection.
  • Current or planned treatment with immunosuppressive therapy, including systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent) starting at Visit 0 and continuously until 28 days after Dose 3 (Visit 9), for an autoimmune disease. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
  • Have received or plan to receive blood/plasma products or immunoglobulin from 120 days before Dose 1 and continuously until 28 days after Dose 3 (Visit 9).
  • Use of any non-trial IMP within 28 days before Dose 1 (Visit 1) in this trial or planned receipt continuously until Visit 12 in this trial, or participation in the active treatment phase of another interventional clinical trial.
  • Are subject to exclusion periods from another investigational clinical trial.
  • Are breastfeeding or are planning pregnancy or to father children during the trial or within 90 days after Dose 3 in this trial.
  • Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade >1 abnormality at Visit 0.
  • Note: Trial participants with Grade ≤1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator.
  • Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, make the participant inappropriate for the trial.
  • Have a history of alcohol abuse or drug addiction within 1 year before Visit 0, or have a history (within the past 5 years) of substance abuse which in the opinion of the investigator, could compromise their wellbeing if they participate as participants in the trial, or that could prevent, limit, or confound the protocol specified assessments.
  • Are vulnerable individuals as per International Council on Harmonisation (ICH) E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

  • emovis GmbH

    Berlin, 10629

  • CRS Clinical Research Services Berlin GmbH

    Berlin, 13627

  • CRS Clinical Research Services Mannheim GmbH

    Mannheim, 68167

Other trials in Germany

About this study

Official title: A Phase Ia, Randomized, Placebo-controlled, Double-blind, Dose-finding Evaluation Trial to Describe the Safety, Reactogenicity, and Immunogenicity of Two Investigational Vaccines Against Tuberculosis in IGRA-negative, BCG naïve Subjects

This randomized, placebo-controlled, double-blind, safety and dose-finding Phase Ia trial will evaluate four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule.

Read the detailed description

Enrollment for BNT164a1 and BNT164b1 will be conducted independently, and in parallel. The trial will enroll participants divided into eight dose groups by dose level (4 dose levels per vaccine, i.e., BNT164a1 and BNT164b1) who will be randomized 7:1 to BNT164 (BNT164a1 or BNT164b1):placebo. The trial will use a staggered dose escalation schema with sentinel participants for Dose 1 in all dose groups. The first dose escalation decision will be made based on data from the first 8 participants. The second dose escalation decision will take into account all safety data from participants enrolled in that group. All safety data, e.g., from the 16 participants in the first dose level, will be used for making decisions at higher dose levels.

Conditions
Tuberculosis
Being tested
BNT164a1, BNT164b1, Placebo
Keywords
Prevention of active tuberculosis, RNA Vaccine, Vaccine
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BNT164a1Biological

    Multi-antigen ribonucleic acid (RNA) vaccine for active immunization against tuberculosis administered as intramuscular injection

  • BNT164b1Biological

    Multi-antigen ribonucleic acid (RNA) vaccine for active immunization against tuberculosis administered as intramuscular injection

  • PlaceboOther

    Placebo

Study groups in NCT05537038
Study groupRoleWhat they receive
BNT164a1ExperimentalEscalating dose levels
Receives: Biological: BNT164a1
BNT164b1ExperimentalEscalating dose levels
Receives: Biological: BNT164b1
PlaceboExperimentalIsotonic NaCl solution (0.9%)
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of solicited local reactions (pain, erythema/redness, induration/swelling) at the injection site up to 7 days after each dose

    Measured: Up to 7 days after each dose

  2. Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue, muscle pain and joint pain, chills, and fever) up to 7 days after each dose

    Measured: Up to 7 days after each dose

  3. Proportion of participants with at least one adverse event (AE) occurring from each dose to 28 days after each dose

    Measured: From Day 1 until Day 197

  4. Proportion of participants with at least one AE occurring from Dose 1 to 28 days post-Dose 3

    Measured: From Day 1 until Day 197

  5. Proportion of participants with at least one serious adverse event (SAE) or medically attended adverse event (MAAE) occurring from Dose 1 up to 168 days post-Dose 3

    Measured: From Day 1 until Day 337

  6. Number of AEs from Dose 1 to 28 days post-Dose 3

    Measured: From Day 1 until Day 197

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2022
  2. Study start18 Apr 2023
  3. Primary completion6 Jun 2025
  4. Study completion8 Dec 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05537038
Sponsor's protocol ID
BNT164-01
Other IDs
2022-000911-29, 2023-509515-89-00, 2023
Status last verified
Dec 2025
First submitted
8 Sep 2022
Last updated
22 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Agrawal N, Ates LS, Schille SA, Chaturvedi A, Vogt J, Vukovic N, Dulberger CL, Vogel AB, Diekmann J, Diken M, Sahin U. mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models. Nat Immunol. 2026 Aug;27(8):1653-1665. doi: 10.1038/s41590-026-02545-z. Epub 2026 Jun 12.

    PubMed 42286358

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BNT164a1 and BNT164b1 in people with Tuberculosis, run by BioNTech SE at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of solicited local reactions (pain, erythema/redness, induration/swelling) at the injection site up to 7 days after each dose (time frame: Up to 7 days after each dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05537038, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2025.

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