Safety and Immune Responses After Vaccination With Two Investigational RNA-based Vaccines Against Tuberculosis in BCG Vaccinated Volunteers
Study Details
Study Description
Brief Summary
This randomized, placebo-controlled, observer-blind, safety and dose-finding Phase I trial will be conducted in countries in Africa, including Republic of South Africa. This trial will evaluate three dose levels of the BNT164 investigational vaccines (BNT164a1 and BNT164b1) to select a safe and tolerable dose in a three-dose schedule.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Enrollment for BNT164a1 and BNT164b1 will be conducted independently, and in parallel. The trial will enroll participants into six cohorts by dose level who will be stratified by interferon gamma release assay (IGRA) status and then randomized 5:1 for BNT164 (BNT164a1 or BNT164b1):placebo. The trial will use a staggered dose escalation schema with sentinel participants for Dose 1 in all cohorts.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BNT164a1 Escalating dose levels |
Biological: BNT164a1
Multi-antigen ribonucleic acid (RNA) vaccine for active immunization against tuberculosis administered as intramuscular injection
|
| Experimental: BNT164b1 Escalating dose levels |
Biological: BNT614b1
Multi-antigen ribonucleic acid (RNA) vaccine for active immunization against tuberculosis administered as intramuscular injection
|
| Placebo Comparator: Placebo Isotonic NaCl solution (0.9%) |
Other: Placebo
Placebo
|
Outcome Measures
Primary Outcome Measures
- Frequency of solicited local reactions (pain, erythema/redness, induration/swelling) at the injection site up to 7 days after each dose [Up to 7 days after each dose]
- Frequency of solicited systemic reactions (vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, and fever) up to 7 days after each dose [Up to 7 days after each dose]
- Proportion of participants with at least one adverse event (AE) occurring from Dose 1 to 28 days post-Dose 3 [From Day 1 until Day 197]
- Proportion of participants with at least one serious adverse event (SAE), adverse event of special interest (AESI), or medically attended adverse event (MAAE) occurring from Dose 1 up to 168 days post-Dose 3 [From Day 1 until Day 337]
- Number of adverse events (AEs) from Dose 1 to 28 days post-Dose 3 [From Day 1 until Day 197]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Have given informed consent by signing and dating an informed consent form (ICF) before initiation of any trial-specific procedures.
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Are 18 to 55 years of age inclusive and have a body mass index over 18.5 kg/m2 and under 35 kg/m2 and weigh at least 50 kg.
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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.
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Have a history of Bacillus Calmette-Guérin (BCG) vaccination.
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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]).
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Hemoglobin ≥12.0 g/dL for volunteers who were born female, ≥13.0 g/dL for volunteers who were born male.
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Volunteers of childbearing potential (VOCBP) must have a negative urine pregnancy test at Visit 0 and before each investigational medicinal product (IMP) dose. Volunteers born female that are postmenopausal or permanently sterilized (verified by medical records) will not be considered VOCBP and therefore are not required to undergo pregnancy testing.
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VOCBP who agree to practice a highly effective form of contraception and to require their male partners to use condoms with a spermicidal agent, starting at Visit 0 and continuously until 60 days after receiving their last IMP injection in this trial.
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VOCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during trial, starting at Visit 0 and continuously until 60 days after receiving their last IMP injection in this trial.
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Men who are sexually active with a partner of childbearing potential and have not had a vasectomy who agree to use condoms with a spermicidal agent 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.
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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.
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Negative alcohol breath test at Visit 0 or Visit 1.
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Negative drugs of abuse (for amphetamines, benzodiazepines, barbiturates, cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, tricyclic antidepressants) result at Visit 0 or Visit 1.
Exclusion Criteria:
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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.
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Any bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
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Baseline clinical screening questionnaire positive for pulmonary tuberculosis disease or history of sputum sample positive for tuberculosis, or history of treatment for active or latent tuberculosis.
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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).
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Current or history of cardiovascular diseases, e.g., myocardial infarction, congestive heart failure, cardiomyopathy, or clinically significant arrhythmias, myocarditis, or pericarditis.
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History of syncope (fainting) in association with administration of injectable vaccines.
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Known or suspected immunodeficiency.
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History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMP.
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Positive test result at Visit 0 or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
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History of previous administration of experimental tuberculosis vaccines, or any planned non-trial vaccinations within 28 days before Visit 0 and continuously until 28 days after Dose 3 (Visit 10).
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Current or planned treatment with immunosuppressive therapy, including systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥5 mg/day of prednisone or equivalent) starting at Visit 0 and continuously until 28 days after Dose 3 (Visit 10), for an autoimmune disease. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
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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 10).
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Use of any non-trial IMP within 28 days before Dose 1 in this trial (Visit 1) or planned receipt continuously until Visit 12 in this trial, or participation in the active treatment phase of another interventional clinical trial.
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Are subject to exclusion periods from another investigational clinical trial.
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Are breastfeeding or are planning pregnancy within 60 days after Dose 3 in this trial or to father children during the trial or within 90 days after Dose 3 in this trial.
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Any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥1 abnormality at Visit 0.
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Note: Trial participants with any stable Grade 1 abnormalities (according to the toxicity grading scale) may be considered eligible at the discretion of the investigator. A "stable" Grade 1 laboratory abnormality is defined as a report of Grade 1 on an initial blood sample that remains Grade ≤1 upon repeat testing on a second sample from the same participant.
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History of psychiatric illness, including alcohol abuse or drug addiction within 1 year before Visit 0, or a history (within the past 5 years) of substance abuse or known medical, psychological, or social conditions 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.
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- BioNTech SE
Investigators
- Study Director: BioNTech Responsible Person, BioNTech SE
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BNT164-02