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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: AZD1222; Drug: 0.9% (w/v) saline

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Japan, 810-0021
    • Research Site
  • Hachioji-shi, Japan, 192-0046
    • Research Site
  • Minato-ku, Japan, 108-0075
    • Research Site
  • Sumida-ku, Japan, 130-0004
    • Research Site
  • Toshima-ku, Japan, 171-0021
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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:

1. Known past laboratory-confirmed SARS-CoV-2 infection
2. Positive SARS-CoV-2 RT PCR test at screening
3. Seropositivity to SARS-CoV-2 at screening.
4. Significant infection or other illness, including fever > 37.8°C on the day prior to or day randomization
5. History of Guillain-Barré syndrome
6. 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)
7. History of allergy to any component of the vaccine
8. Any history of angioedema
9. Any history of anaphylaxis
10. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and uterine cervical carcinoma in situ)
11. History of serious psychiatric condition likely to affect participation in the study
12. Bleeding disorder (eg, factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
13. Suspected or known current alcohol or drug dependency
14. 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
15. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part I; 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; For subjects in part 1 will have that route of Administration as Intramuscular, 5 × 1010 vp (nominal, ± 1.5 × 1010 vp) on V2
Placebo Comparator: Part II; 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; For subjects in placebo will have that route of Administration as Intramuscular 0.9% (w/v) saline on V2 and V6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroresponse to the Spike (S) Antigen of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay	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.	Baseline (Day 1) and Day 57
Number of Participants With Local Solicited Adverse Events (AE)	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.	From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days
Number of Participants With Systemic Solicited AEs	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.	From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days
Number of Participants With AEs, Serious AEs (SAE) and Adverse Event of Special Interest (AESI) Occurring Post Each Dose of Study Vaccination	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.	From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters	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).	From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroresponse to the Receptor-Binding Domain (RBD) Antigen of AZD1222 as Measured by MSD Serology Assay	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.	Baseline (Day 1) and Day 57
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay	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.	Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay	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.	Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365
Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies (nAb) of AZD1222 as Measured by Pseudo-Neutralization Assay	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.	Baseline (Day 1) and Day 57
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay	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.	Baseline (Day 1) and Days 29, 57, 183, and 365
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay	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.	Baseline (Day 1) and Days 29, 57, 183, and 365
Number of Participants With SAEs and AESIs Occurring Throughout the Study	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.	From Day 1 up to final DCO of 17 January 2022, up to a maximum of 365 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: IQVIA Pty Ltd

Publications and helpful links

General Publications

• Asano M, Okada H, Itoh Y, Hirata H, Ishikawa K, Yoshida E, Matsui A, Kelly EJ, Shoemaker K, Olsson U, Vekemans J. Immunogenicity and safety of AZD1222 (ChAdOx1 nCoV-19) against SARS-CoV-2 in Japan: a double-blind, randomized controlled phase 1/2 trial. Int J Infect Dis. 2022 Jan;114:165-174. doi: 10.1016/j.ijid.2021.10.030. Epub 2021 Oct 22.

Helpful Links

• Redacted SAP
• Redacted CSP
• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2020
• Primary Completion (Actual): November 22, 2021
• Study Completion (Actual): November 22, 2021

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19 Vaccine
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: D8111C00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No