临床试验/NCT05004181

NCT05004181已完成2 期

A Phase II Trial to Evaluate the Safety and Immunogenicity of SARS-CoV-2 Monovalent and Multivalent RNA-based Vaccines in Healthy Subjects

BioNTech SE35 个研究点分布在 4 个国家目标入组 1,380 人开始时间: 2021年8月25日最近更新: 2024年11月22日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: BioNTech SE
入组人数: 1,380
试验地点: 35
主要终点: All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This trial consisted of three parts, Part A, Part B, and Part C, and evaluated the safety and immunogenicity of a third (booster) injection of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and the safety and immunogenicity of a third booster injection of the monovalent vaccine BNT162b2 (B.1.617.2) or BNT162b2 (B.1.1.7), in participants who had received two doses of the parent vaccine BNT162b2 at 30 µg, at least 6 months after the second dose of BNT162b2. It also evaluated the safety and immunogenicity of a three-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior Coronavirus Disease 2019 (COVID-19) vaccination. In addition, the safety and immunogenicity of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a third or fourth vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARS-CoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine-experienced participants.

详细描述

Trial participants in Part A were assigned to one of 6 cohorts (Cohort 1-6). Trial participants in Part B were assigned to one of 3 cohorts (Cohort 1, 4, and 6). Trial participants in Part C were randomized in a 2:2:1 ratio into 3 cohorts (Cohort 7-9).

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

入排标准

年龄范围: 18 Years 至 85 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•Had given informed consent by signing the informed consent form (ICF) before initiation of any trial-specific procedures.
•Volunteers who at the time of consent were:
•Part A: 18 to 55 years old.
•Part B and Part C: 18 to 85 years old (~60% should be 18 to 55 years old and ~40% 56 to 85 years old).
•For Cohorts 1 to 5: In Part A, who had received BNT162b2 vaccine (30 µg, two-dose regimen) in either a clinical trial or as part of the governmental vaccination programs at least 6 months before Visit
•Participants who were currently enrolled in the Phase III BNT162-02 / C4591001 (NCT04368728) trial, had already been unblinded, and had previously received two doses of BNT162b2 at least 6 months earlier could be included (for Cohorts 1 and 4 in Part B, prior enrollment and dosing in the C4591001 trial was mandatory). At enrollment into Part B of this trial, their participation in the C4591001 trial was terminated. Participants should have not had experienced COVID-19 based on medical history.
•For Cohort 6: Were COVID-19 vaccine-naïve and had not experienced COVID-19 based on their medical history.
•Were willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other trial procedures.
•Were overall healthy at Visit 0 in the clinical judgment of the investigator based on the medical history, clinical assessment (including physical examination, vital signs, blood and urine clinical laboratory tests, 12-lead electrocardiogram (ECG), and oral swab for Nucleic Acid Amplification-based Test (NAAT)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing).
•Note: Healthy volunteers with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 12 weeks before Visit 0, could be included.
•Note: Volunteers who had hepatitis C (HCV) infection, but had completed curative treatment based on the medical history could be included. Volunteers who had or have hepatitis B (HBV) or human immunodeficiency virus (HIV) based on the medical history could not be included.
•Agreed not to enroll in another trial of an Investigational Medicinal Product (IMP), starting after Visit 0 and continuously until the last planned visit in this trial.
•Women of childbearing potential (WOCBP) had to test negative in a urine beta-human chorionic gonadotropin (β-HCG) test at Visits 0 and
•WOCBP had to agree to practice a highly effective form of contraception starting at Visit 0 and continuously until 28 days after their last IMP administration in this trial.
•WOCBP had to confirm that they practiced an acceptable form of contraception for the 14 days prior to Visit
•WOCBP had to agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
•Men who are sexually active with a WOCBP and had not had a vasectomy had to agree to use a highly effective form of contraception with their female partner of childbearing potential starting after Visit 0 and continuously until 28 days after their last IMP injection in this trial.
•Men had to be willing to refrain from sperm donation, starting after Visit 0 and continuously until 28 days after their last vaccination.
•For Part C, Cohorts 7, 8, and 9: Had received two or three documented doses of any authorized COVID-19 RNA-based vaccine (e.g., BNT162b2 [Comirnaty] or the Moderna vaccine [Spikevax]) prior to being diagnosed with SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).
•Note: The interval between the last COVID-19 RNA-based vaccine administered and randomization should have been >4 months. The latest prior diagnosed SARS-CoV-2 infection should have been at least 2 months before randomization. The latest SARS-CoV-2 infection should have been documented with a result from a NAAT (as a preferable option). In case no historic NAAT result was available proving prior SARS-CoV-2 infection, the local positive result of SARS-CoV-2 N-binding antibodies done at screening was sufficient.

排除标准

•Any existing condition which could have affected vaccine injection and/or assessment of local reactions assessment, e.g., tattoos, severe scars, etc.
•Any bleeding diathesis or condition associated with prolonged bleeding that could have, in the opinion of the investigator, contraindicated intramuscular injection.
•Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that, in the investigator's judgment, made the participant inappropriate for the trial.
•Any current febrile illness (body temperature ≥38.0°C/≥100.4°F) or other acute illness within 48 h prior to Day 1/IMP injection in this trial.
•Any current or history of cardiovascular diseases, e.g., myocarditis, pericarditis, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, unless such disease was not considered relevant for participation in this trial in the investigator's judgment.
•History of COVID-19 and/or clinical (based on COVID-19 symptoms/signs alone, if a SARS CoV 2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS CoV 2 NAAT result) evidence of prior infection with SARS CoV 2 at screening (Visit 0).
•Note: not applicable for Part C.
•History of Guillain-Barré syndrome.
•Known or suspected immunodeficiency.
•History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any component of the trial IMPs.
•History or known allergy, hypersensitivity, or intolerance to the trial IMP including any excipients of the IMPs in this trial.
•Had received any SARS CoV 2 vaccination other than BNT162b2 (30 µg BNT162b2 given as a course of two doses approximately 21 days apart).
•Note: not applicable for Part C.
•Had received a live or live attenuated vaccine within 28 days prior to Day 1/IMP injection.
•Had received any other vaccines within 14 days before or after any IMP injection, e.g., influenza, tetanus, pneumococcal, hepatitis A or B. When possible standard of care vaccinations should been planned with the trial IMP administrations in mind.
•Individuals who received treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids were administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout this trial. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids were permitted.
•Receipt of blood/plasma products or immunoglobulin, from 60 days before IMP administration or planned receipt throughout this trial.
•Participation in other trials involving IMP within 28 days or 5 half-lives (whichever was longer) prior to Visit 1 and/or during trial participation, besides participation in trials with BNT162b
•Were pregnant or breastfeeding or are planning pregnancy within 28 days after last IMP treatment.
•Were vulnerable individuals as per International Conference 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.
•For Part C, Cohorts 7, 8, and 9: Vaccination with other non-RNA or unauthorized COVID-19 vaccines.
•For Part C, Cohorts 7, 8, and 9: Vaccination with any COVID-19 vaccine after SARS-CoV-2 infection from January 2022 onwards (and limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections).

研究组 & 干预措施

Part A - Cohort 3: 18 to 55 years of age

Experimental

Participants received1 dose of BNT162b2 (B.1.1.7) of 30 µg.

干预措施: Monovalent BNT162b2 (B.1.1.7) (Biological)

Part A - Cohort 1: 18 to 55 years of age

Experimental

Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

干预措施: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) (Biological)

Part A - Cohort 2: 18 to 55 years of age

Experimental

Participants received 2 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

干预措施: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) (Biological)

Part A - Cohort 4: 18 to 55 years of age

Experimental

Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.

干预措施: Monovalent BNT162b2 (B.1.617.2) (Biological)

Part A - Cohort 5: 18 to 55 years of age

Experimental

Participants received 1 dose of BNT162b2 of 30 µg.

干预措施: BNT162b2 (Biological)

Part A - Cohort 6: 18 to 55 years of age

Experimental

Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

干预措施: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) (Biological)

Part B - Cohort 1: 18 to 85 years of age

Experimental

Participants received 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

干预措施: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) (Biological)

Part B - Cohort 4: 18 to 85 years of age

Experimental

Participants received 1 dose of BNT162b2 (B.1.617.2) of 30 µg.

干预措施: Monovalent BNT162b2 (B.1.617.2) (Biological)

Part B - Cohort 6: 18 to 85 years of age

Experimental

Participants received 3 doses of BNT162b2 (B.1.1.7 + B.1.617.2) of 30 µg.

干预措施: Multivalent BNT162b2 (B.1.1.7 + B.1.617.2) (Biological)

Part C - Cohort 7: 18 to 85 years of age

Experimental

Participants received 1 dose of BNT162b2 (B.1.1.529.1) of 30 µg.

干预措施: Monovalent BNT162b2 (B.1.1.529.1) (Biological)

Part C - Cohort 8: 18 to 85 years of age

Experimental

Participants received 1 dose of BNT162b2 of 30 µg.

干预措施: BNT162b2 (Biological)

Part C - Cohort 9: 18 to 85 years of age

Other

Participants received no vaccination within 3 months after Visit 1.

干预措施: Observational (Other)

结局指标

主要结局

All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/Redness, Induration/Swelling)

时间窗: from Day 1 to Day 7 after each IMP dose

Local reactions of any grade are reported. Local reactions were graded using criteria based on the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

时间窗: from Day 1 to Day 7 after each IMP dose

Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the guidance given in the US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C are not included in the analysis. Subjects in Cohort 9 did not receive a vaccination and are not included in this analysis.

All Parts - Percentage of Participants Reporting Adverse Events (AEs)

时间窗: Dose 1 up to 1 month after each dose (all parts)

An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, dose 2, dose 3 and overall summaries are based upon the number of participants who received the respective IMP dose.

All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

时间窗: Dose 1 up to 6 months after the last dose

An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE is defined as TESAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event is considered as treatment-emergent unless the partial onset date information or complete or partial end date confirms the onset date or the event end prior to the first dose of IMP.

Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (NCT04368728) Trial