Study of AZD1222 for the Prevention of COVID-19 in Japan

Study Overview
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Brief Summary
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The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Currently, there are no licensed preventions available against COVID-19 and accelerated vaccine development is urgently needed. A safe and effective vaccine for COVID 19 prevention would have significant global public health impact.

Official Title
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A Phase I/II Randomized, Double-blind, Placebo-controlled Multicentre Study in Participants Aged 18 Years or Older to Determine the Safety and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: AZD1222
* Drug: 0.9% (w/v) saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged 18 to 55 years (Cohort A and C), aged 56 to 69 years (Subcohorts B1 and D1), or aged ≥ 70 years (Subcohorts B2 and D2) Exclusion Criteria: Known past laboratory-confirmed SARS-CoV-2 infection Positive SARS-CoV-2 RT PCR test at screening Seropositivity to SARS-CoV-2 at screening. Significant infection or other illness, including fever > 37.8°C on the day prior to or day randomization History of Guillain-Barré syndrome Any confirmed or suspected immunosuppressive or immunodeficient state; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting ≤ 14 days) History of allergy to any component of the vaccine Any history of angioedema Any history of anaphylaxis Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and uterine cervical carcinoma in situ) History of serious psychiatric condition likely to affect participation in the study Bleeding disorder (eg, factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture Suspected or known current alcohol or drug dependency Any other significant disease, disorder or finding which may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study or impair interpretation of the study data Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed)

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part I<br>Cohort C will include healthy participants aged 18 to 55 years. Cohort D will include healthy elderly participants aged ≥ 56 years. In Cohort D, the elderly population is further divided into 2 different age subgroups; aged 56 to 69 years (Subcohort D1) and aged ≥ 70 years (Subcohort D2). At least 30% of participants in Cohort D will be secured for participants with age ≥ 70 years. | Drug: AZD1222<br>* For subjects in part 1 will have that route of Administration as Intramuscular, 5 × 1010 vp (nominal, ± 1.5 × 1010 vp) on V2<br>|
| Placebo Comparator: Part II<br>Cohort C will include healthy participants aged 18 to 55 years. Cohort D will include healthy elderly participants aged ≥ 56 years. In Cohort D, the elderly population is further divided into 2 different age subgroups; aged 56 to 69 years (Subcohort D1) and aged ≥ 70 years (Subcohort D2). At least 30% of participants in Cohort D will be secured for participants with age ≥ 70 years. | Drug: 0.9% (w/v) saline<br>* For subjects in placebo will have that route of Administration as Intramuscular 0.9% (w/v) saline on V2 and V6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who have a post treatment seroresponse to the spike antigens of AZD1222 | The primary immunogenicity endpoint is the proportion of participants who have a post treatment seroresponse (≥ 4-fold rise in titres from Day 1 baseline value) to the Spike antigens of AZD1222 (MSD serology assay) at Day 57 , and will be calculated along with its 95% CI based on the Clopper-Pearson method in each treatment groups in each cohort (C, and D) and also Subcohorts D1, and D2 separately. | Day 57 | 
| The incidence of local and systemic solicited reactogenicity signs and symptoms for 7 days following throughout vaccination | The incidence of local and systemic solicited reactogenicity signs and symptoms for 7 days following throughout vaccination (Day 1 to 8). | Day 1 to 8 | 
| The incidence of local and systemic solicited reactogenicity signs and symptoms for 7 days following throughout vaccination | The incidence of local and systemic solicited reactogenicity signs and symptoms for 7 days following throughout vaccination (Day 29 to 36). | Day 29 to 36 | 
| The incidence of AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) | The incidence of AEs, serious adverse events (SAEs) and adverse events of special interest (AESIs) collected from Day 1 through Day 57. | Day 1 through Day 57 | 
| Biochemistry; change from baseline for blood chemistry measures | The change from baseline for blood chemistry measures (Creatinine in U/L ,Bilirubin in mg/dL, ALP in U/L, AST in U/L, ALT in U/L, Albumin in g/dL, Potassium in mEq/L, Calcium in mg/dL Sodium mEq/L, Creatine Kinase in U/L) | Day 8, Day 29, Day 36, and Day 57 | 
| Haematology; change from baseline for hematology/hemostasis measures | The change from baseline for hematology measures (Hb in g/dL, Leukocyte in /uL, Leukocyte differential count in /uL and Platelet count in /uL) | Day 8, Day 29, Day 36, and Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who have a post treatment | The proportion of participants who have a post treatment seroresponse (≥ 4-fold rise in titres from Day 1 baseline value) to RBD antigens of AZD1222 (MSD serology assay) at Day 57, and will be calculated along with its 95% CI based on the Clopper-Pearson method in each treatment groups in each cohort (C, and D) and also Subcohorts D1, and D2 separately. | Day 57 | 
| Genometric mean titres and genometric mean fold rise | Geometric mean titres and geometric mean fold rise [Time Frame: Day 57 ] Geometric mean titres (GMT) and geometric mean fold rise (GMFR) of immunogenicity to Spike and RBD antigen of AZD1222 (MSD serology assay) with its 95% CI will be computed at each time point in each treatment arm in each cohort (C, and D) and also in Subcohorts D1, and D2 separately. | Day 57 | 
| Proportion of participants who have a post treatment seroresponse to AZD1222 as measured by SARS-CoV-2 nAbs | The proportion of participants who have a post treatment seroresponse to AZD1222 as measured by SARS-CoV-2 nAbs [Time Frame: Day 57 ] The proportion of participants who have a post treatment seroresponse (≥ 4-fold rise in titres from Day 1 baseline value) to AZD1222 as measured by SARS-CoV02 nAbs (wild-type assay or pseudoneutralisation assay) at Day 57, and will be calculated along with its 95% CI based on the Clopper-Pearson method in each treatment groups in each cohort (C, and D) and also Subcohorts D1, and D2 separately. | Day 57 | 
| The incidence of serious adverse events (SAEs) and adverse events of specisl interest (AESIs) collected from Day1 through Day365 | The incidence of serious adverse events (SAEs) and adverse events of special interest (AESIs) collected from Day 1 through Day 365. | Day 1 through Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Vaccine