A PHASE 1, OPEN-LABEL DOSE-FINDING STUDY TO EVALUATE SAFETY, TOLERABILITY, AND IMMUNOGENICITY AND PHASE 2/3 PLACEBO-CONTROLLED, OBSERVER-BLINDED SAFETY, TOLERABILITY, AND IMMUNOGENICITY STUDY OF A SARS-COV-2 RNA VACCINE CANDIDATE AGAINST COVID-19 IN HEALTHY CHILDREN
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- BioNTech SE
- 入组人数
- 11,837
- 试验地点
- 263
- 主要终点
- In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥2 to <5 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study
研究概览
简要总结
This is a Phase 1/2/3 study in healthy children.
Dependent upon safety and/or immunogenicity data generated during the course of this study, and the resulting assessment of benefit-risk, the safety, tolerability, and immunogenicity of BNT162b2 in participants <6 months of age may subsequently be evaluated.
详细描述
Phase 1 Dose-Finding
Is the open-label dose-finding portion of the study that will evaluate safety, tolerability, and immunogenicity of BNT162b2 administered on a 2-dose (separated by approximately 21 days) schedule in up to 3 age groups (participants ≥5 to <12 years, ≥2 to <5 years, and ≥6 months to <2 years of age).
Dose finding is being initiated in this study in participants ≥5 to <12 years of age based on the acceptable blinded safety assessment of the 30-µg dose in 12- to 15-year-olds in the C4591001 study.
The purpose of Phase 1 is to identify preferred dose level(s) of BNT162b2 from up to 3 different dose levels in each age group.
Dependent upon safety and/or immunogenicity data generated during the course of this study, it is possible that dose levels may not be started, may be terminated early, and/or may be added with dose levels below the lowest stated dose.
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
- 6 Months 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female participants ≥6 months to <12 years of age, at the time of randomization, at Visit 1 for the dose-finding/selected-dose evaluation. For the obtaining-serum-samples-for-potential-troponin I-testing portion of the study: Male or female participants between ≥5 and <16 years of age.
- •Participants' parent(s)/legal guardian(s) and participants, as age appropriate, who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •Healthy participants who are determined by medical history, physical examination, and clinical judgment of the investigator to be eligible for inclusion in the study.
- •Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in the therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included.
- •Participants are expected to be available for the duration of the study and whose parent(s)/legal guardian can be contacted by telephone during study participation.
- •Negative urine pregnancy test for female participants who are biologically capable of having children.
- •Female participant of childbearing potential or male participant able to father children who is willing to use a highly effective method of contraception as outlined in this protocol for at least 28 days after the last dose of study intervention if at risk of pregnancy with her/his partner; or female participant not of childbearing potential or male participant not able to father children.
- •The participant or participant's parent(s)/legal guardian is capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol. Depending on the age of the participant and according to local requirements, participants will also be asked to provide assent as appropriate (verbal or written).
排除标准
- •Phase 1 only: Past 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) diagnosis of COVID
- •Phase 1 only: Known infection with HIV, HCV, or HBV.
- •Receipt of medications intended to prevent COVID-
- •Previous or current diagnosis of MIS-C.
- •Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Note: This includes both conditions that may increase the risk associated with study intervention administration or a condition that may interfere with the interpretation of study results
- •History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
- •Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
- •Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to systemic lupus erythematosus. Note: Stable type 1 diabetes and hypothyroidism are permitted.
- •Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
- •Female who is pregnant or breastfeeding.
- •Previous vaccination with any coronavirus vaccine.
- •Individuals who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.
- •Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19 from 90 days before study intervention administration, or planned receipt throughout the study.
- •Participation in other studies involving study intervention within 28 days prior to study entry and/or during study participation.
- •Previous participation in other studies involving study intervention containing LNPs.
- •Participants who are direct descendants (child or grandchild) of investigational site staff members or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
研究组 & 干预措施
Placebo, ≥6 Months to <2 Years (3-dose regimen)
干预措施: Placebo (Other)
Placebo, ≥2 to <5 Years (3-dose regimen)
干预措施: Placebo (Other)
High-Dose, ≥2 to <5 Years
High-Dose, (30mcg), 2 doses 21 days apart
干预措施: BNT162b2 30mcg (Biological)
Low/Mid-Dose, ≥6 Months to <2 Years
Low/Mid-Dose, (10mcg), 2 doses 21 days apart
干预措施: Biological/Vaccine: BNT162b2 10mcg (Biological)
Low/Mid-Dose, ≥5 to <12 Years (Troponin I Testing)
Low/Mid-Dose (10mcg), 3 doses
干预措施: Biological/Vaccine: BNT162b2 10mcg (Biological)
Placebo, ≥5 to <12 Years (Troponin I Testing)
干预措施: Placebo (Other)
Low-Dose, ≥6 Months to <2 Years (3-dose regimen)
Low-Dose (3mcg), 3 doses
干预措施: Biological/Vaccine: BNT162b2 3mcg (Biological)
Low-Dose, ≥2 to <5 Years (3-dose regimen)
Low-Dose (3mcg), 3 doses
干预措施: Biological/Vaccine: BNT162b2 3mcg (Biological)
Placebo, ≥2 to <5 Years
干预措施: Placebo (Other)
Placebo, ≥5 to <12 Years
干预措施: Placebo (Other)
Low/Mid-Dose, ≥5 to <12 Years
Low/Mid-Dose (10mcg), 2 doses 21 days apart
干预措施: Biological/Vaccine: BNT162b2 10mcg (Biological)
Mid-Dose, ≥5 to <12 Years
Mid-Dose, (20mcg), 2 doses 21 days apart
干预措施: BNT162b2 20mcg (Biological)
High-Dose, ≥5 to <12 Years
High-Dose (30mcg), 2 doses 21 days apart
干预措施: BNT162b2 30mcg (Biological)
Low/Mid-Dose, ≥2 to < 5 Years
Low/Mid-Dose (10mcg), 2 doses 21 days apart
干预措施: Biological/Vaccine: BNT162b2 10mcg (Biological)
Mid-Dose, ≥2 to <5 Years
Mid-Dose, (20mcg), 2 doses 21 days apart
干预措施: BNT162b2 20mcg (Biological)
Mid-Dose, ≥6 Months to <2 Years
Mid-Dose, (20mcg), 2 doses 21 days apart
干预措施: BNT162b2 20mcg (Biological)
High-Dose, ≥6 Months to <2 Years
High-Dose, (30mcg), 2 doses 21 days apart
干预措施: BNT162b2 30mcg (Biological)
Placebo, ≥6 Months to <2 Years
干预措施: Placebo (Other)
Low-Dose, ≥6 Months to <2 Years
Low-Dose (3mcg), 2 doses 21 doses apart
干预措施: Biological/Vaccine: BNT162b2 3mcg (Biological)
Low-Dose, ≥2 to <5 Years
Low-Dose (3mcg), 2 doses 21 days apart
干预措施: Biological/Vaccine: BNT162b2 3mcg (Biological)
High-Dose, 12 to <16 Years (Troponin I Testing)
High-Dose (30mcg), 3 doses
干预措施: BNT162b2 30mcg (Biological)
结局指标
主要结局
In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥2 to <5 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study
时间窗: 1 month after the second dose
As measured at the central laboratory
Percentage of participants in Phase 1 reporting local reactions
时间窗: for 7 days after Dose 1 and Dose 2
Pain or tenderness at the injection site, redness and swelling as reported on electronic diaries.
Percentage of participants in Phase 1 reporting serious adverse events
时间窗: from Dose 1 through 6 months after the last dose
As elicited by investigational site staff
Percentage of participants in Phase 2/3 reporting adverse events
时间窗: from Dose 1 through 1 month after the last dose
As elicited by investigational site staff
Percentage of participants in Phase 2/3 reporting serious adverse events
时间窗: from Dose 1 through 6 months after the last dose
As elicited by investigational site staff
Percentage of participants in Phase 2/3 reporting systemic events
时间窗: for 7 days after Dose 1 and Dose 2
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, new or worsened joint pain, decreased appetite, drowsiness, and irritability as reported on electronic diaries
Percentage of participants in Phase 1 reporting adverse events
时间窗: from Dose 1 through 1 month after the last dose
As elicited by investigational site staff
In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥5 to <12 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study
时间窗: 1 month after the second dose
As measured at the central laboratory
Percentage of participants in Phase 1 reporting systemic events
时间窗: for 7 days after Dose 1 and Dose 2
Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened join pain, decreased appetite drowsiness, and irritability as reported on electronic diaries
Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥2 to <5 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 years in the C4591001 study
时间窗: 1 month after the second dose
As measured at the central laboratory
Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥6 months to <2 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 in C4591001 study
时间窗: 1 month after the second dose
As measured at the central laboratory
Percentage of participants in Phase 2/3 reporting local reaction
时间窗: for 7 days after Dose 1 and Dose 2
Pain or tenderness at the injection site, redness and swelling as reported on electronic diaries.
Ph 2/3 selected-dose (2-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 2 doses in participants ≥5 to <12 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in participants 16 to 25 years in the C4591001 study
时间窗: 1 month after the second dose
As measured at the central laboratory
In Phase 2/3 selected-dose (2-dose series), the difference in percentages of participants with seroresponse in participants ≥6 months to <2 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001
时间窗: 1 month after the second dose
As measured at the central laboratory
Ph 2/3 selected-dose (3-dose), immunobridging SARS-CoV-2 serum neutralizing titers after 3 doses in participants ≥6 months to <2 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in C4591001 participants 16 to 25 in study after 2 doses
时间窗: 1 month after the third dose
As measured at the central laboratory
In Phase 2/3 selected-dose (3-dose series), the difference in percentages of participants with seroresponse in participants ≥2 to <5 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001 study
时间窗: 1 month after the third dose
As measured at the central laboratory
In Phase 2/3 selected-dose (3-dose series), the difference in percentages of participants with seroresponse in participants ≥6 months to <2 years of age and participants 16 to 25 years of age from Phase 2/3 of the C4591001
时间窗: 1 month after the third dose
As measured at the central laboratory
Ph 2/3 selected-dose (3-dose series), immunobridging of SARS-CoV-2 serum neutralizing titers after 3 doses in participants ≥2 to <5 years to the geometric mean of SARS-CoV-2 serum neutralizing titers in C4591001 participants 16 to 25 years after 2 doses
时间窗: 1 month after the third dose
As measured at the central laboratory
次要结局
- In evaluable Phase 2/3 participants at selected dose level in each age group, Geometric Mean Titers of SARS-CoV-2 neutralizing titers with no serological or virological evidence of past SARS-CoV-2 infection(At baseline (before Dose 1) and 1, 6, 12 (for the original BNT162b2 group only), and 24 (for the original BNT162b2 group only) months after Dose 2)
- Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥5 to <12 years of age with successful immunobridging, with and without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group(From 7 days after the second dose to prior to third dose)
- Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥6 months to <5 years of age (3-dose series), evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group(From 7 days after the third dose)
- Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥5 to <12 years of age with successful immunobridging, without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group(From 7 days after the second dose to prior to third dose)
- In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs(At each time point)
- In evaluable Phase 2/3 participants at the dose level selected in each age group, Geometric Mean Fold Ratio in SARS-CoV-2 serum neutralizing titer from before vaccination to each subsequent time point(From before Dose 1 to each subsequent time point after Dose 2)
- Ratio of confirmed COVID-19 illness, Phase 2/3 selected-dose participants ≥6 months to <5 years of age (3-dose series), with and without evidence of prior SARS-CoV-2 infection for the active vaccine group to the placebo group(From 7 days after the third dose)