A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, AND OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE AGAINST COVID-19 IN HEALTHY JAPANESE ADULTS
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- BioNTech SE
- 入组人数
- 160
- 试验地点
- 4
- 主要终点
- Percentage of Participants With Adverse Events (AEs) From Dose 1 up to 1 Month After Dose 2
研究概览
简要总结
This is a Phase 1/2, randomized, placebo-controlled, and observer-blind study in healthy Japanese adults.
The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19:
- As 2 doses, separated by 21 days
- At a single dose level
- In adults 20 to 85 years of age
详细描述
From protocol amendment 3, this study is transitioned from a clinical trial to a postmarketing study (Phase 4) according to the Japanese regulation, because BNT162b2 was approved by the Ministry of Health, Labour and Welfare on 14 February 2021.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Japanese male or female participants between the ages of 20 and 85 years, inclusive, at randomization.
- •Participants who are willing and able to comply with all scheduled visits, vaccination 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.
- •Capable of giving personal signed informed consent.
排除标准
- •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.
- •Known infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).
- •History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
- •Receipt of medications intended to prevent COVID-
- •Previous confirmed diagnosis of COVID-
- •Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
- •Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
- •Women who are 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.
- •Receipt of blood/plasma products or immunoglobulin, from 60 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 lipid nanoparticles.
- •Subset only: Any screening hematology and/or blood chemistry laboratory value that meets the definition of a ≥ Grade 1 abnormality.
- •Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs) From Dose 1 up to 1 Month After Dose 2
时间窗: Dose 1 up to 1 month after Dose 2
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of participants with AEs and the associated 95% confidence interval (CI) based on the Clopper and Pearson method was presented. Only AEs collected by non-systematic assessment (i.e. excluding local reactions and systemic events) were reported in this outcome measure.
Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 1 Day After Dose 1 by Age Category
时间窗: Within 1 day after Dose 1
The pre-defined criteria for laboratory parameters included: hemoglobin (HGB), hematocrit, erythrocytes(ery.) less than (\<)0.8\* lower limit of normal (LLN); ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*upper limit of normal (ULN); platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Percentage of participants with abnormal hematology and chemistry laboratory values by age categories 20 to 64 years and 65 to 85 years were reported in this outcome measure. Categories with at least 1 non-zero data values were reported.
Percentage of Participants With Local Reactions by Maximum Severity Within 7 Days After Dose 2
时间窗: Within 7 days after Dose 2
Local reactions included pain at injection site, redness and swelling and were recorded by participants in an e-diary. Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 cm and graded as mild: \> 2.0 to 5.0 cm, moderate: \>5.0 to 10.0 cm, severe: \>10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Events were classified as Grade 4 based on study investigator's judgement. Maximum severity was the highest grade within 7 days after vaccination among severity grades where the answers were neither "no" nor missing for at least 1 day.
Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 7 Days After Dose 1 by Age Category
时间窗: Within 7 days after Dose 1
The pre-defined criteria for laboratory parameters included: HGB, hematocrit, ery. \<0.8\* LLN; ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*ULN; platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Percentage of participants with abnormal hematology and chemistry laboratory values by age categories 20 to 64 years and 65 to 85 years were reported in this outcome measure. Categories with at least 1 non-zero data values were reported.
Percentage of Participants With Serious Adverse Events (SAEs) From Dose 1 up to 12 Months After Dose 2
时间窗: Dose 1 up to 12 months after Dose 2
SAE was defined as 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 or significant disability/incapacity; resulted in congenital anomaly/birth defect or considered an important medical event. Percentage of participants with SAEs and the associated 95% CI based on the Clopper and Pearson method was presented.
Geometric Mean Fold Rises (GMFRs) of SARS-CoV-2 Neutralizing Titers From Before Vaccination to 1 Month After Dose 2
时间窗: Before vaccination up to 1 month after Dose 2
GMFR was defined as the result after vaccination divided by the result before vaccination. GMFR and the corresponding 2-sided 95% CIs was calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution). GMFR of SARS-CoV-2 NT50 was reported in this outcome measure.
Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Baseline to 7 Days After Dose 1 by Age Category
时间窗: From baseline (observation prior to Dose 1) up to 7 days after Dose 1
Hematology parameters included: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, WBC decrease, WBC increase. Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in grade from baseline to 7 days after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Geometric Mean Titers (GMTs) of SARS-CoV-2 Neutralizing Titers at 1 Month After Dose 2
时间窗: 1 month after Dose 2
GMT of SARS-CoV-2 neutralizing titer was calculated by exponentiating the mean logarithm of the titers and the corresponding 95% confidence interval (CI) was based on the Student's t distribution. GMT of SARS-CoV-2 neutralization titer 50% (NT50) was reported in this outcome measure.
Percentage of Participants With Local Reactions by Maximum Severity Within 7 Days After Dose 1
时间窗: Within 7 days after Dose 1
Local reactions included pain at injection site, redness and swelling and were recorded by participants in an electronic diary (e-diary). Redness and swelling were measured and recorded in measuring device units. 1 measuring device unit =0.5 centimeter (cm) and graded as mild: greater than (\>) 2.0 to 5.0 cm, moderate: \>5.0 to 10.0 cm, severe: \>10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis for redness and necrosis for swelling. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Events were classified as Grade 4 based on study investigator's judgement. Maximum severity was the highest grade within 7 days after vaccination among severity grades where the answers were neither "no" nor missing for at least 1 day.
Percentage of Participants With Systemic Events by Maximum Severity Within 7 Days After Dose 1
时间窗: Within 7 days after Dose 1
Systemic events were recorded by participants in e-diary. Fever was categorized as greater than or equal to (\>=)37.5 to 38.4 degrees(deg) Celsius(C), \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours(h), moderate: \>2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Events were classified as Grade 4 potentially life threatening (emergency room visit or hospitalization) based on study investigator's judgement. Maximum severity=highest grade within 7 days after vaccination among severity grades where the answers were neither "no" nor missing for at least 1 day.
Percentage of Participants With Systemic Events by Maximum Severity Within 7 Days After Dose 2
时间窗: Within 7 days after Dose 2
Systemic events were recorded by participants in an e-diary. Fever was categorized as \>= 37.5 to 38.4 deg C, \>38.4 to 38.9 deg C, \>38.9 to 40.0 deg C and \>40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: \>2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. Events were classified as Grade 4 potentially life threatening (emergency room visit or hospitalization) based on study investigator's judgement. Maximum severity=highest grade within 7 days after vaccination among severity grades where the answers were neither "no" nor missing for at least 1 day.
Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 7 Days After Dose 2 by Age Category
时间窗: Within 7 days after Dose 2
The pre-defined criteria for laboratory parameters included: HGB, hematocrit, ery. \<0.8\* LLN; ery. mean corpuscular volume, ery. mean corpuscular hemoglobin, ery. mean corpuscular HGB concentration \<0.9\*LLN and \>1.1\*ULN; platelets \<0.5\*LLN and \>1.75\*ULN; leukocytes \<0.6\*LLN and \>1.5\*ULN; lymphocytes, neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes \>1.2\*ULN; bilirubin \>1.5\*ULN; aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase \>3.0\*ULN; urea nitrogen, creatinine \>1.3\*ULN. Categories with at least 1 non-zero data value were reported (only 65-85 years: Lymphocytes category was reported).
Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Before Dose 2 to 7 Days After Dose 2 by Age Category
时间窗: Before Dose 2 up to 7 days after Dose 2
Hematology parameters included: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, WBC decrease, WBC increase. Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3= severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in grade from before dose 2 to 7 days after dose 2 were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Baseline to 1 Day After Dose 1 by Age Category
时间窗: From baseline (observation prior to Dose 1) up to 1 day after Dose 1
Hematology parameters: hemoglobin, eosinophils, lymphocytes decrease, neutrophil decrease, platelets decrease, white blood cell (WBC) decrease, WBC increase. Chemistry parameters: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, bilirubin increased, creatinine increased, blood urea nitrogen. Laboratory abnormalities were graded by toxicity grading scale for healthy adult volunteers enrolled in preventive vaccine clinical trials as grade 1=mild; grade 2=moderate; grade 3=severe and grade 4=potentially life-threatening. Percentage of participants with shift in hematology and chemistry laboratory values by age categories (20 to 64 years and 65 to 85 years) were reported in this outcome measure. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. normal to normal) were not reported.
次要结局
- GMFRs of SARS-CoV-2 Neutralizing Titers Before Vaccination to 21 Days After Dose 1; 7 and 14 Days and 6 and 12 Months After Dose 2(NT50: Before vaccination up to 21 days after Dose 1; 7 and 14 days and 6 and 12 months after Dose 2; NT90: Before vaccination up to 21 days after Dose 1; 7 and 14 days after Dose 2)
- GMTs of SARS-CoV-2 Neutralizing Titers at Baseline, 21 Days After Dose 1; 7 and 14 Days and 6 and 12 Months After Dose 2(NT50: Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days and 6 and 12 months after Dose 2; NT90: Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days after Dose 2)
- GMTs of SARS-CoV-2 Neutralizing Titers at Baseline, 21 Days After Dose 1; 7 and 14 Days and 1, 6 and 12 Months After Dose 2 in Participants With or Without Confirmed COVID-19 Before Dose 2(Baseline (observation prior to Dose 1), 21 days after Dose 1; 7 and 14 days and 1, 6 and 12 months after Dose 2)
- GMFRs of SARS-CoV-2 Neutralizing Titers Before Vaccination to 21 Days After Dose 1; 7 and 14 Days and 1, 6 and 12 Months After Dose 2 in Participants With or Without Confirmed COVID-19 Before Dose 2(Before vaccination up to 21 days after Dose 1; 7 and 14 days after Dose 2 and 1, 6 and 12 months after Dose 2)