Originally, the study was planned to include two parts, i.e., Part A and Part B, however Part B was skipped due to changes in the overall clinical development plan. The conducted Part A was a dose-finding part to investigate the optimal dose, allowing dose adjustments upwards and downwards in younger participants. Doses tested in older participants were chosen based on acceptability of dosing in younger participants.
This study was a multi-site, Phase I/II, open-label, dose-escalation study. The study
included the first in human dose and dose ranging groups in healthy younger participants
(aged 18 to 55 years [yrs]) and older participants (aged 56 to 85 yrs). The conducted Part A
followed a dose escalation design. Discretionary dose de-escalation and refinement was also
planned. Study participants with the first-in-human [FIH] immunization and any subsequent
dose escalation cohorts were immunized using a sentinel dosing/subject staggering. For any
dose de-escalation or dose-refinement cohorts in younger adults, i.e., cohorts with doses
lower than previously tested, participants were dosed using a subject staggering process.
Cohorts in older participants were optional and dependent on acceptability of dosing in
younger participants. Part A consisted of a treatment phase (screening to Visit 7) and a
follow-up phase (Visits 8 to 10).
Biological: BNT162b3
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection (Prime/Boost (P/B) regimen).
Inclusion Criteria:
- Have given informed consent by signing the informed consent form (ICF) before
initiation of any trial-specific procedures.
- They must be willing and able to comply with scheduled visits, treatment schedule,
laboratory tests, lifestyle restrictions (e.g., to practice social distancing and to
follow good practices to reduce their chances of being infected or spreading
COVID-19), and other requirements of the trial.
- They must be able to understand and follow trial-related instructions.
- For younger adult cohorts, volunteers must be aged 18 to 55 years, have a body mass
index over 19 kg/m^2 and under 30 kg/m^2 (i.e., be neither underweight nor obese), and
weigh at least 50 kg at Visit 0.
OR For older adult cohorts, volunteers must be aged 56 to 85 years, have a body mass index
over 19 kg/m^2 and under 30 kg/m^2 (i.e., be neither underweight nor obese), and weigh at
least 50 kg at Visit 0.
- They must be healthy, in the clinical judgment of the investigator, based on medical
history, physical examination, 12-lead electrocardiogram (ECG), vital signs
(systolic/diastolic blood pressure, pulse rate, body temperature, respiratory rate),
and clinical laboratory tests (blood chemistry, hematology, and urine chemistry) at
Visit 0.
- Women of childbearing potential (WOCBP) must have a negative beta-human chorionic
gonadotropin urine test at Visit 0 and Visit 1. Women that are postmenopausal or
permanently sterilized will be considered as not having reproductive potential.
- WOCBP must agree to practice a highly effective form of contraception during the
trial, starting after Visit 0 and continuously until 60 days after receiving the last
immunization. WOCBP must agree to require their male partners to use condoms during
sexual contact (unless male partners are sterilized or infertile).
- WOCBP must confirm that they practiced at least one highly effective form of
contraception for the 14 days prior to Visit 0.
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during trial, starting after Visit 0 and continuously until 60 days after
receiving the last immunization.
- Men who are sexually active with a WOCBP and have not had a vasectomy must agree to
practice a highly effective form of contraception with their female partner of
childbearing potential during the trial, starting after Visit 0 and continuously until
60 days after receiving the last immunization.
- Men must be willing to refrain from sperm donation, starting after Visit 0 and
continuously until 60 days after receiving the last immunization.
- They must have confirmation of their health insurance coverage prior to Visit 0.
- They must agree to not be vaccinated during the trial, starting after Visit 0 and
continuously until 28 days after receiving the last immunization.
Exclusion Criteria:
- Have had any acute illness, as determined by the investigator, with or without fever,
within 72 hours prior to the first immunization. An acute illness which is nearly
resolved with only minor residual symptoms remaining is allowable if, in the opinion
of the investigator, the residual symptoms will not compromise their well-being if
they participate as trial subjects in the trial, or that could prevent, limit, or
confound the protocol-specified assessments.
- Are breastfeeding on the day of Visit 0 or who plan to breastfeed during the trial,
starting after Visit 0 and continuously until at least 90 days after receiving the
last immunization.
- Have a known allergy, hypersensitivity, or intolerance to the planned investigational
medicinal product (IMP) including any excipients of the IMP.
- Had any medical condition or any major surgery (e.g., requiring general anesthesia)
within the past 5 years which, in the opinion of the investigator, could compromise
their well-being if they participate as trial subjects in the trial, or that could
prevent, limit, or confound the protocol-specified assessments.
- Have any surgery planned during the trial, starting after Visit 0 and continuously
until at least 90 days after receiving the last immunization.
- Had any chronic use (more than 21 continuous days) of any systemic medications,
including immunosuppressants or other immune-modifying drugs, within the 6 months
prior to Visit 0 unless in the opinion of the investigator, the medication would not
prevent, limit, or confound the protocol-specified assessments or could compromise
subject safety.
- Received any vaccination within the 28 days prior to Visit 0.
- Had administration of any immunoglobulins and/or any blood products within the 3
months prior to Visit 0.
- Had administration of another IMP including vaccines within 60 days or 5 half-lives
(whichever is longer), prior to Visit 0.
- Have a known history or a positive test of any of human immunodeficiency virus (HIV) 1
or 2, Hepatitis B, or Hepatitis C, within the 30 days prior to Visit 0.
- Have a positive polymerase chain reaction (PCR)-based test for severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) within the 30 days prior to Visit 1.
- Have a positive drugs of abuse (for amphetamines, benzodiazepines, barbiturates,
cocaine, cannabinoids, opiates, methadone, methamphetamines, phencyclidine, and
tricyclic antidepressants) result at Visit 0 or Visit 1.
- Have a positive breath alcohol test at Visit 0 or Visit 1.
- Previously participated in an investigational trial involving lipid nanoparticles.
- Are subject to exclusion periods from other investigational trials or simultaneous
participation in another clinical trial.
- Have any affiliation with the trial site (e.g., are close relative of the investigator
or dependent person, such as an employee or student of the trial site).
- Have 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 well-being if they participate as trial subjects in the trial, or
that could prevent, limit, or confound the protocol-specified assessments.
- Have a history of hypersensitivity or serious reactions to previous vaccinations.
- Have a history of Guillain-Barré Syndrome within 6 weeks following a previous
vaccination.
- Have a history of narcolepsy.
- Have history of alcohol abuse or drug addiction within 1 year before Visit 0.
- Have a history of or suspected immunosuppressive condition, acquired or congenital, as
determined by medical history and/or physical examination at Visit 0.
- Have any abnormality or permanent body art (e.g., tattoo) that, in the opinion of the
investigator, would obstruct the ability to observe local reactions at the injection
site.
- Have had any blood loss >450 mL, e.g., due to donation of blood or blood products or
injury, within the 7 days prior to Visit 0 or plan to donate blood during the trial,
starting after Visit 0 and continuously until at least 7 days after receiving the last
immunization.
- Symptoms of COVID-19, e.g., respiratory symptoms, fever, cough, shortness of breath
and breathing difficulties.
- Have had contact with persons diagnosed with COVID-19 or who tested positive for
SARS-CoV-2 by any diagnostic test within the 30 days prior to Visit 1.
- Are soldiers, subjects in detention, contract research organization (CRO) or sponsor
staff or their family members.
- Regular receipt of inhaled/nebulized corticosteroids.
- Have a condition known to put them at high risk for severe COVID-19, including those
with any of the following risk factors:
- Cancer
- COPD (chronic obstructive pulmonary disease)
- Immunocompromised state (weakened immune system) from solid organ transplant
- Obesity (BMI of 30 or higher)
- Serious heart conditions, such as heart failure, coronary artery disease, or
cardiomyopathies
- Sickle cell disease
- Diabetes mellitus
- Hypertension
- Asthma
- Chronic liver disease
- Known Stage 3 or worse chronic kidney disease (glomerular filtration rate <60
mL/min/1.73 m^2)
- Anticipating the need for immunosuppressive treatment within the next 6 months
- Resident in a long-term facility
- Current vaping or smoking (occasional smoking is acceptable)
- History of chronic smoking within the prior year
Contract Research Organization
Berlin, Germany
Contract Research Organization
Mannheim, Germany
BioNTech Responsible Person, Study Director
BioNTech SE