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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Covid-19
- Sponsor
- BioNTech SE
- Enrollment
- 96
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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).
Investigators
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
- •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
- •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
- •Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin urine test at Visit 0 and Visit
- •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
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 participants 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 participants 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 participant safety.
- •Received any vaccination within the 28 days prior to Visit
- •Had administration of any immunoglobulins and/or any blood products within the 3 months prior to Visit
- •Had administration of another IMP including vaccines within 60 days or 5 half-lives (whichever is longer), prior to Visit
- •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
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Fold Increase in Functional Antibody Titers(From 51 to up to 387 days following first IMP dose)
- Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline(From 51 to up to 387 days following first IMP dose)
- Functional Antibody Responses(From 51 to up to 387 days following first IMP dose)