A Trial Investigating the Safety and Effects of One BNT162 Vaccine Against COVID-19 in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04537949
• Recruitment Status: Completed
• First Posted: September 3, 2020
• Results First Posted: March 24, 2022
• Last Update Posted: March 24, 2022
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: September 2, 2020
• First Posted Date: September 3, 2020
• Results First Submitted Date: February 14, 2022
• Results First Posted Date: March 24, 2022
• Last Update Posted Date: March 24, 2022
• Actual Study Start Date: September 9, 2020
• Actual Primary Completion Date: March 12, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2022)

• Number of Participants With Solicited Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling) Recorded up to 7 Days After Each IMP Dose [ Time Frame: From Day 1 to Day 8 for Prime Immunization and from Day 22 to Day 29 for Boost Immunization ]
  Solicited local reactions at the injection site (pain, tenderness, erythema/redness, and induration/swelling) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of local reactions was based on the participant's assessments via daily solicited reports in the participant diaries.
• Number of Participants With Solicited Systemic Reactions (Nausea, Vomiting, Diarrhea, Headache, Fatigue, Myalgia, Arthralgia, Chills, Loss of Appetite, Malaise, and Fever) Recorded up to 7 Days After Each IMP Dose [ Time Frame: From Day 1 to Day 8 for Prime Immunization and from Day 22 to Day 29 for Boost Immunization ]
  Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) were monitored and graded using criteria based on the guidance given in US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials". The reporting of systemic reactions was based on the participant's assessments via daily solicited reports in the participant diaries.
• The Percentage of Participants With at Least 1 Unsolicited Treatment Emergent Adverse Event (TEAE) Occurring After Prime Immunization up to Boost Immunization or 28 Days After Prime Immunization [ Time Frame: 28 days following first IMP dose or up to second IMP dose (whichever was first) ]
  Treatment emergent adverse events (TEAEs) were analyzed by age group, dose level, and for each IMP dose. The number and percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade >=3 TEAE) using the Safety Set.
• The Percentage of Participants With at Least 1 Unsolicited TEAE Occurring up to 28 Days After Boost Immunization or After Prime Immunization (if no Boost Immunization) [ Time Frame: 28 days following second IMP dose or first IMP dose (if no second IMP dose as given) ]
  Treatment emergent adverse events (TEAEs) were analyzed by age group, dose level, and for each IMP dose. The percentage of participants reporting at least one TEAE was summarized by adverse event types (any TEAE and any grade >=3 TEAE) using the Safety Set.

Original Primary Outcome Measures (submitted: September 2, 2020)

• Solicited local reactions at the injection site (pain/tenderness, erythema/redness, induration/swelling) recorded up to 7±1 days after each immunization. [ Time Frame: up to 7 days following each dose administration ]
• Solicited systemic reactions (nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) recorded up to 7±1 days after each immunization. [ Time Frame: up to 7 days following each dose administration ]
• The proportion of subjects with at least 1 unsolicited treatment emergent adverse event (TEAE) occurring up to 21±2 days after the prime immunization. [ Time Frame: 21 days following dose administration ]
• The proportion of subjects with at least 1 unsolicited TEAE occurring up to 28±4 days after the boost immunization. [ Time Frame: 28 days following dose administration ]

Current Secondary Outcome Measures (submitted: March 22, 2022)

• Functional Antibody Responses [ Time Frame: up to 50 days following first IMP dose ]
  At 7 and 21 days after primary immunization and at 7, 14, 21, 28 days after boost immunization.
• Fold Increase in Functional Antibody Titers [ Time Frame: up to 50 days following first IMP dose ]
  At 7 and 21 days after primary immunization and at 7, 14, 21, and 28 days after the boost immunization.
• Number of Subjects With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline [ Time Frame: up to 50 days following first IMP dose ]
  At 7 and 21 days after primary immunization and at 7, 14, 21, and 28 days after the boost immunization.
• Functional Antibody Responses [ Time Frame: From 51 to up to 365 days following first IMP dose ]
  At 63, 162, 365 days after boost immunization.
• Fold Increase in Functional Antibody Titers [ Time Frame: From 51 to up to 365 days following first IMP dose ]
  At 63, 162, 365 days after boost immunization.
• Number of Subjects With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline [ Time Frame: From 51 to up to 365 days following first IMP dose ]
  At 63, 162, 365 days after boost immunization.

Original Secondary Outcome Measures (submitted: September 2, 2020)

• Functional antibody responses. [ Time Frame: up to 365 days following dose administration ]
  At 7±1 days and 21±2 days after primary immunization and at 21±2 days, 28±4 days, 63±5 days, 162±7 days, and 365±14 days after the boost immunization.
• Fold increase in functional antibody titers. [ Time Frame: up to 365 days following dose administration ]
  At 7±1 days and 21±2 days after primary immunization and at 21±2 days, 28±4 days, 63±5 days, 162±7 days, and 365±14 days after the boost immunization.
• Number of subjects with seroconversion defined as a minimum of 4-fold increase of functional antibody titers as compared to baseline. [ Time Frame: up to 365 days following dose administration ]
  At 7±1 days and 21±2 days after primary immunization and at 21±2 days, 28±4 days, 63±5 days, 162±7 days, and 365±14 days after the boost immunization.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial Investigating the Safety and Effects of One BNT162 Vaccine Against COVID-19 in Healthy Adults
• Official Title: A Multi-site, Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of a Prophylactic SARS-CoV-2 RNA Vaccine (BNT162b3) Against COVID-19 Using Different Dosing Regimens in Healthy Adults
• Brief Summary: 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.
• Detailed Description: 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).
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Covid-19
• Protection Against COVID-19

Intervention

Biological: BNT162b3

Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection (Prime/Boost (P/B) regimen).

Study Arms

• Experimental: Part A participants aged 18 to 55 years
  Escalating dose levels
  Intervention: Biological: BNT162b3
• Experimental: Part A participants aged 56 to 85 years (optional)
  Escalating dose levels
  Intervention: Biological: BNT162b3

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 25, 2021): 96
• Original Estimated Enrollment (submitted: September 2, 2020): 120
• Actual Study Completion Date: February 7, 2022
• Actual Primary Completion Date: March 12, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT04537949
• Other Study ID Numbers: BNT162-04; 2020-003267-26 ( EudraCT Number ); U1111-1254-4840 ( Other Identifier: WHO Universal Trial Number (UTN) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: BioNTech RNA Pharmaceuticals GmbH
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: BioNTech RNA Pharmaceuticals GmbH
• Collaborators: Not Provided

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: March 2022