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

NCT05547464 | Active Not Recruiting Phase 1

• 3 other identifiers: BNT164-02DOH-27-052023-8662PACTR202505818080160
• Study Type: interventional
• Target: 497
• Locations: 2 countries
• Sites: 8

Brief Summary

This is a two-part randomized, placebo-controlled, observer-blind, safety and dose-finding Phase Ib/IIa study. This study will evaluate up to four dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule. This study includes: Part A (Phase Ib) and Part B (Phase IIa).

Conditions

Tuberculosis

Keywords

Prevention of tuberculosis; RNA Vaccine; Vaccine; TB

Outcome Measures

Primary Outcomes (6)

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

  Part A and Part B

  Up to 7 days after each dose

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

  Part A and Part B

  Up to 7 days after each dose

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

  Part A and Part B

  From each dose up to 28 days after each dose

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

  Part A and Part B

  From Dose 1 up to 28 days post-Dose 3

• Proportion of participants with at least one serious AE or AE of special interest occurring from Dose 1 up to 168 days post-Dose 3

  Part A and Part B. In Part A, from Dose 1 up to 168 days post-Dose 3. In Part B, from Dose 1 up to 28 days post- Dose 3.

  From Dose 1 up to 168 days post-Dose 3

• Number of unsolicited AEs from Dose 1 to 28 days post-Dose 3

  Part A and Part B

  From Dose 1 up to 28 days post-Dose 3

Study Arms (7)

Part A: BNT164a1

EXPERIMENTAL

Escalating dose levels

Biological: BNT164a1

Part A: BNT164b1

EXPERIMENTAL

Escalating dose levels

Biological: BNT164b1

Part B: BNT164a1 Dose level (DL) 1

EXPERIMENTAL

Biological: BNT164a1

Part B: BNT164a1 DL 2

EXPERIMENTAL

Biological: BNT164a1

Part B: BNT164b1 DL 1

EXPERIMENTAL

Biological: BNT164b1

Part B: BNT164b1 DL 2

EXPERIMENTAL

Biological: BNT164b1

Placebo

PLACEBO COMPARATOR

Isotonic sodium chloride (NaCl) solution (0.9%)

Other: Placebo

Interventions

BNT164a1 BIOLOGICAL

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

Part A: BNT164a1; Part B: BNT164a1 DL 2; Part B: BNT164a1 Dose level (DL) 1

BNT164b1 BIOLOGICAL

Multi-antigen RNA vaccine for active immunization against tuberculosis administered as intramuscular injection

Part A: BNT164b1; Part B: BNT164b1 DL 1; Part B: BNT164b1 DL 2

Placebo OTHER

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Have given informed consent by signing and dating an informed consent form before initiation of any study-specific procedures.
• Are 18 to 55 years of age inclusive (in Part A) or 18 years of age or older (in Part B) and have a body mass index 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 study. This includes that they are able to understand and follow study-related instructions.
• In Part A only: Have a reported history or evidence of (scar) of Bacillus Calmette-Guérin (BCG) vaccination.
• Are overall healthy in the clinical judgment of the investigator based on the medical history and clinical assessment (including physical examination, vital signs, clinical laboratory tests, and 12-lead electrocardiogram \[ECG\]).
• Hemoglobin ≥12.0 g/dL (in Part A) and ≥11.0 g/dL (in Part B) for volunteers who were born female, ≥13.0 g/dL (in Part A) and ≥12.5 g/dL (in Part B) for volunteers who were born male.
• Volunteers of childbearing potential (VOCBP) must have a negative serum beta-human chorionic gonadotropin pregnancy test at Visit 0 and negative urine pregnancy test results before each IMP administration. Volunteers born female that are postmenopausal (confirmed by follicle stimulating hormone) or permanently sterilized (verified by medical records) will not be considered VOCBP.
• 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 study.
• VOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during study, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this study.
• Men who are sexually active with a partner of childbearing potential and have not had a vasectomy who agree to use condoms and to ask their sexual partners to practice a highly effective form of contraception during the study, starting at Visit 0 and continuously until 90 days after receiving their last IMP injection in this study.
• 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 study.

You may not qualify if:

• 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.
• Baseline clinical screening questionnaire positive for pulmonary TB disease or history of sputum sample positive for TB, or history of treatment for TB infection or disease.
• Current febrile illness (body temperature ≥38.0°C) or other acute illness at Visit 0.
• Current or history of the following medical conditions:
• Cardiovascular diseases, e.g., myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias, myocarditis, or pericarditis.
• Hypertension
• If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well controlled blood pressure is defined as consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤150 mm Hg systolic and ≤90 mm Hg diastolic at enrollment.
• If a person does not have a history of elevated blood pressure or hypertension previously or during screening, also exclude for systolic blood pressure ≥150 mm Hg at enrollment or diastolic blood pressure ≥100 mm Hg at enrollment.
• Diabetes mellitus type 1 or type 2 cases requiring medication.
• Thyroidectomy, or thyroid disease requiring medication during the last 12 months.
• Malignancy within 5 years of Visit 0, excluding localized basal or squamous cell cancer.
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions), or (in Part B only) are on a medication determined by the investigator to increase the risk of bleeding.
• Seizure disorder: History of seizure(s) within past 3 years. Also exclude if participant has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• An abnormal screening or Visit 1 ECG (i.e., showing the corrected QT interval by Fridericia (QTcF) \>450 ms; significant ST-T wave changes suggestive of myocardial ischemia or of an acute or indeterminate-age myocardial infarction; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions; complete right or left bundle branch block \[QRS \>120 ms\]; second- or third-degree atrioventricular block); or other clinically significant abnormalities on the ECG at the investigator's discretion.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (8)

Centro de Investigação em Saúde de Manhiça (CISM) (recruiting participants for Part B only)

Manhiça, 1929, Mozambique

Location

Centro de Investigação e Treino em Saúde da Polana Caniço (CISPOC) (recruiting participants for Part B only)

Maputo, 1102, Mozambique

Location

CAPRISA eThekweni Clinical Research Site

Berea, 4001, South Africa

Location

South African Tuberculosis Vaccine Initiative SATVI

Cape Town, 6850, South Africa

Location

Centre for Lung Infection and Immunity UCT Lung Institute

Cape Town, 7700, South Africa

Location

Desmond Tutu Health Foundation - Masiphumele Research Office

Cape Town, 7975, South Africa

Location

Africa Health Research Institute (AHRI)

Mtubatuba, 3935, South Africa

Location

The Aurum Institute Tembisa CRC Clinic 4

Tembisa, 1632, South Africa

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Observer-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 21, 2022
• Study Start: July 31, 2023
• Primary Completion: March 12, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

MO (2); ZA (6)