Originally, the study was planned to include two parts, i.e., Part A and Part B, however Part B was cancelled due to changes in the overall clinical development plan. The objectives originally described for Part B have been implemented in the ongoing development via a pivotal Phase I/II/III trial BNT162-02/C4591001 (ClinicalTrials.gov NCT: 04368728). The conducted Part A was a dose-finding part to investigate the optimal dose of four different vaccines (BNT162a1, BNT162b1, BNT162b2, and BNT162c2), allowing dose adjustments upwards and downwards in younger participants. Doses tested in older participants and expansion cohorts were chosen based on acceptability of dosing in younger participants. The vaccines BNT162a1, BNT162b1, BNT162b2, and BNT162c2 were administered using a Prime/Boost (P/B) regimen with two doses given \~21 days apart. The vaccine BNT162c2 was also administered using a Single dose (SD) regimen. Four additional expansion cohorts (cohorts 11, 12, 13, and 14) aged from 18 to 85 years received BNT162b2 using a P/B regimen only. In cohort 11, participants received BNT162b2 using one 3 μg prime dose (Dose 1) and one 30 μg boost dose (Dose 2) of BNT162b2. Participants in cohorts 12, 13, and 14 received two doses of BNT162b2 30 µg, each.
This study was a multi-site, Phase I/II, open-label, dose-escalation study. The study included the first-in-human (FIH) dose and dose ranging groups for all four vaccines in healthy younger participants (aged 18 to 55 years \[years\]) and older participants (aged 56 to 85 years). The conducted Part A followed a dose escalation design. Discretionary dose de-escalation and refinement was also planned. Study participants with the 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 and a follow-up phase. For the BNT162a1 3 µg arm, the Safety Review Committee (SRC) decided to stop dosing after 6 treated participants and to not administer the boost immunization (Dose 2). For the BNT162b1 60 µg arm, the SRC decided to not administer the boost immunization (Dose 2) for the 12 participants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
512
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Anti-viral RNA vaccine for active immunization against COVID-19 administered as intramuscular injection.
Contract Research Organization
Berlin, Germany
Universitäts Klinikum
Frankfurt am Main, Germany
Universitäts Klinikum
Heidelberg, Germany
Contract Research Organization
Kiel, Germany
Contract Research Organization
Mannheim, Germany
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.
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.
Time frame: From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)
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.
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.
Time frame: From Day 1 to Day 8 for Dose 1 (Prime Immunization) and from Day 22 to Day 29 for Dose 2 (Boost Immunization)
The Percentage of Participants With at Least 1 Unsolicited Treatment Emergent Adverse Event (TEAE) Occurring After Dose 1 (Prime Immunization) up to Dose 2 (Boost Immunization) or 28 Days After Dose 1.
TEAEs without AEs based on solicited reporting via diaries, were analyzed by vaccine, 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.
Time frame: 28 days following Dose 1 or up to Dose 2 (whichever was first)
The Percentage of Participants With at Least 1 Unsolicited TEAE Occurring After Dose 1 up to 28 Days After Dose 2 (Boost Immunization) or After Dose 1 (Prime Immunization) (if no Dose 2)
TEAEs, without AEs based on solicited reporting via diaries, were analyzed by vaccine, 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.
Time frame: 28 days following Dose 2 or Dose 1 (if no Dose 2 was given)
Functional Antibody Responses (Titers) for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)
At Day 1 (Baseline = Pre-Prime Immunization) and at 7 and 21 days after Dose 1 (Prime Immunization) and at 7, 21, 28, 63, and 162 days after Dose 2 (Boost Immunization).
Time frame: up to 183 days following Dose 1
Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)
At 7 and 21 days after Dose 1 (Prime Immunization) and at 7, 21, 28, 63, and 162 days after Dose 2 (Boost Immunization).
Time frame: up to 183 days following Dose 1
Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162a1, BNT162b1, BNT162b2 (Younger and Older Dose Ranging Cohorts), and BNT162c2 (P/B)
At 7 and 21 days after Dose 1 (Prime Immunization) and at 7, 21, 28, 63, and 162 days after Dose 2 (Boost Immunization).
Time frame: up to 183 days following Dose 1
Functional Antibody Responses (Titers) for BNT162c2 (SD)
At Day 1 (Baseline = Pre Immunization) and at 7, 21, 28, 42, 84, and 183 days after Dose 1 (Prime Immunization).
Time frame: up to 183 days following Dose 1
Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162c2 (SD)
At 7, 21, 28, 42, 84, and 183 days after Dose 1 (Prime Immunization).
Time frame: up to 183 days following Dose 1
Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162c2 (SD)
At 7, 21, 28, 42, 84, and 183 days after Dose 1 (Prime Immunization).
Time frame: up to 183 days following Dose 1
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Functional Antibody Responses (Titers) for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)
At Day 1 (Baseline = Pre-Prime Immunization) and at 7, 14, and 21 days after Dose 1 (Prime Immunization) and at 7, 14, 21, 28, 63, 162, and 343 days after Dose 2 (Boost Immunization).
Time frame: up to 1 year following Dose 1
Fold Increase in Functional Antibody Titers as Compared to Baseline for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)
At 7, 14, and 21 days after Dose 1 (Prime Immunization) and at 7, 14, 21, 28, 63, 162, and 343 days after Dose 2 (Boost Immunization).
Time frame: up to 1 year following Dose 1
Number of Participants With Seroconversion Defined as a Minimum of 4-fold Increase of Functional Antibody Titers as Compared to Baseline for BNT162b2 (Expansion Cohorts 11, 12, 13, and 14; P/B)
At 7, 14, and 21 days after Dose 1 (Prime Immunization) and at 7, 14, 21, 28, 63, 162, and 343 days after Dose 2 (Boost Immunization).
Time frame: up to 1 year following Dose 1