Study to Evaluate the Safety, Tolerability, and Immunogenicity of an RNA Vaccine Candidate Against COVID-19 in Healthy Japanese Adults

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Biological: BNT162b2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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-19. Previous confirmed diagnosis of COVID-19. 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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BNT162b2<br>BNT162b2 (intramuscular injection) | Biological: BNT162b2<br>* BNT162b2 (intramuscular injection)<br>|
| Placebo Comparator: Placebo<br>Placebo (intramuscular injection) | Other: Placebo<br>* Placebo (intramuscular injection)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Local Reactions by Maximum Severity 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. | Within 7 days after Dose 1 | 
| Percentage of Participants With Local Reactions by Maximum Severity 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. | Within 7 days after Dose 2 | 
| Percentage of Participants With Systemic Events by Maximum Severity 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. | Within 7 days after Dose 1 | 
| Percentage of Participants With Systemic Events by Maximum Severity 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. | Within 7 days after Dose 2 | 
| Percentage of Participants With Adverse Events (AEs) From 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. | Dose 1 up to 1 month after Dose 2 | 
| Percentage of Participants With Serious Adverse Events (SAEs) From 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. | Dose 1 up to 12 months after Dose 2 | 
| Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 1 Day After Dose 1 by Age Category | 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. | Within 1 day after Dose 1 | 
| Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 7 Days After Dose 1 by Age Category | 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. | Within 7 days after Dose 1 | 
| Percentage of Participants With Abnormal Hematology and Chemistry Laboratory Values 7 Days After Dose 2 by Age Category | 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). | Within 7 days after Dose 2 | 
| Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Baseline to 1 Day After Dose 1 by Age Category | 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. | From baseline (observation prior to Dose 1) up to 1 day after Dose 1 | 
| Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Baseline to 7 Days After Dose 1 by Age Category | 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. | From baseline (observation prior to Dose 1) up to 7 days after Dose 1 | 
| Percentage of Participants With Shift in Hematology and Chemistry Laboratory Values From Before Dose 2 to 7 Days After Dose 2 by Age Category | 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. | Before Dose 2 up to 7 days after Dose 2 | 
| Geometric Mean Titers (GMTs) of SARS-CoV-2 Neutralizing Titers at 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. | 1 month after Dose 2 | 
| Geometric Mean Fold Rises (GMFRs) of SARS-CoV-2 Neutralizing Titers From Before Vaccination 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. | Before vaccination up to 1 month after Dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | GMTs of SARS-CoV-2 neutralizing titers were calculated by exponentiating the mean logarithm of the titers and the corresponding 95% CI was based on the Student's t distribution. GMTs of SARS-CoV-2 NT50 and neutralization titer 90% (NT90) were reported in this outcome measure. | 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 | 
| 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 | GMFR was defined as the result after vaccination divided by the result before vaccination. GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution). GMFRs of SARS-CoV-2 NT50 and NT90 were reported in this outcome measure. | 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 1, 6 and 12 Months After Dose 2 in Participants With or Without Confirmed COVID-19 Before Dose 2 | GMTs of SARS-CoV-2 neutralizing titers was planned to be calculated by exponentiating the mean logarithm of the titers and the corresponding 95% CI was based on the Student's t distribution. | 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 | GMFR was defined as the result after vaccination divided by the result before vaccination. GMFRs and the corresponding 2-sided 95% CIs were planned to be calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student's t distribution). | 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 |