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

Phase 1

Completed

Conditions: COVID-19

Interventions: Drug: 0.9% (w/v) saline
Drug: AZD1222

Registration Number: NCT04568031

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 256

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part II	0.9% (w/v) saline	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.
Part I	AZD1222	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Local Solicited Adverse Events (AE)	From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days	Solicited AEs are local or systemic predefined AEs for reactogenicity assessment. Participants were given an axillary thermometer, tape measure, and access to app for the solicited AE eDiary, with instructions on use, along with the emergency 24-hour telephone number to contact the on-call study physician if needed. Participants were instructed to record for 7 days following administration of each dose of AZD1222, the timing and severity of local and systemic solicited AEs, if applicable, and whether medication was taken to relieve the symptoms.
Percentage of Participants With Seroresponse to the Spike (S) Antigen of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay	Baseline (Day 1) and Day 57	Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to the S antigen of AZD1222 as measured by MSD serology assay is reported.
Number of Participants With Systemic Solicited AEs	From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days	Solicited AEs are local or systemic predefined AEs for reactogenicity assessment. Participants were given an axillary thermometer, tape measure, and access to app for the solicited AE eDiary, with instructions on use, along with the emergency 24-hour telephone number to contact the on-call study physician if needed. Participants were instructed to record for 7 days following administration of each dose of AZD1222, the timing and severity of local and systemic solicited AEs, if applicable, and whether medication was taken to relieve the symptoms.
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days	Clinical laboratory values were evaluated for each laboratory parameter as applicable including hematology and clinical chemistry. The baseline was defined as the last non-missing measurement taken prior to the first dose of study vaccination (including unscheduled measurements, if any).
Number of Participants With AEs, Serious AEs (SAE) and Adverse Event of Special Interest (AESI) Occurring Post Each Dose of Study Vaccination	From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days	An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is an AE occurring during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. The AESIs were events of scientific and medical interest specific to the further understanding of the study vaccination safety profile and required close monitoring and rapid communication by the investigators to the sponsor.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With SAEs and AESIs Occurring Throughout the Study	From Day 1 up to final DCO of 17 January 2022, up to a maximum of 365 days	An SAE is an AE occurring during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. The AESIs were events of scientific and medical interest specific to the further understanding of the study vaccination safety profile and required close monitoring and rapid communication by the investigators to the sponsor.
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay	Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365	The fold rise was calculated as the ratio of the post-vaccination titer level to the baseline titer level, where baseline was defined as the last measurement taken before the first dose of study vaccination. The GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay	Baseline (Day 1) and Days 29, 57, 183, and 365	The fold rise was calculated as the ratio of the post-vaccination titer level to the baseline titer level, where baseline was defined as the last measurement taken before the first dose of study vaccination. The GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.
Percentage of Participants With Seroresponse to the Receptor-Binding Domain (RBD) Antigen of AZD1222 as Measured by MSD Serology Assay	Baseline (Day 1) and Day 57	Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to the RBD antigen of AZD1222 as measured by MSD serology assay is reported.
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay	Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365	The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.
Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies (nAb) of AZD1222 as Measured by Pseudo-Neutralization Assay	Baseline (Day 1) and Day 57	Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported.
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay	Baseline (Day 1) and Days 29, 57, 183, and 365	The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.