E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
SARS-COV-2 infection (COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1 To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥18years of age
2 To assess the safety and tolerability of 2 IM doses of AZD1222 compared to placebo in adults ≥18years of age |
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E.2.2 | Secondary objectives of the trial |
1. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection.
2. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of symptomatic COVID-19 using CDC criteria.
3. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of University of Oxford defined symptomatic COVID-19
4. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo in the prevention of COVID-19 in all study participants, regardless of evidence of prior SARS-CoV-2 infection
5. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of severe or critical symptomatic COVID-19.
6. To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19-related Emergency Department visits. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The first participants randomized in each age group, including 1 500 participants 18 to 55years of age, 750 participants 56 to 69years of age, and 750 participants ≥ 70 years of age, will also participate in a substudy assessing the reactogenicity and immunogenicity of AZD1222.
Objectives:
1 To assess the reactogenicity of 2 IM doses of AZD1222 compared to placebo in adults ≥18years of age
2 To assess antibody responses to AZD1222 Santigen following 2 IM doses of AZD1222 or placebo
3 To determine anti-SARS-CoV-2 neutralizing antibody levels in serum following 2 IM doses of AZD1222 or placebo |
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E.3 | Principal inclusion criteria |
- Increased risk of SARS-CoV-2 infection, Defined as adults whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-19, based on available risk assessment contemporaneous to enrollment (believed to be at risk/exposure)
- Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months prior to enrollment |
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E.4 | Principal exclusion criteria |
- Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia
- Any other significant disease, disorder, or finding that 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
- Receipt of, or planned receipt of investigational products indicated for the treatment or prevention of SARS-CoV-2 or COVID-19 Note: For participants who become hospitalized with COVID-19, receipt of licensed treatment options and/orparticipation in investigational treatment studies is permitted |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring ≥ 15 days post second dose of study intervention, in a participant with negative
serostatus at baseline. Participants will be included in the primary endpoint if they have RT-PCR-confirmed SARS-CoV-2 and meet the following criteria at any point from their initial illness visit at the site (Day 1) through their second illness visit (Day 14):
One or more Category A findings OR Two or more Category B findings
Category A:
-Pneumonia diagnosed by chest x-ray, or computed tomography scan
-Oxygen saturation of ≤ 94% on room air or requiring either new initiation or escalation in
supplemental O2
-New or worsening dyspnea/shortness of breath
Category B:
-Fever > 100 °F (> 37.8 °C) or feverishness
-New or worsening cough
-Myalgia/muscle pain
-Fatigue that interferes with activities of daily living
-Vomiting and/or diarrhea (only one finding to be counted toward endpoint definition)
-Anosmia and/or ageusia (only one finding to be counted toward endpoint definition) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Participants are followed through Day360 for symptomatic COVID-19 |
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E.5.2 | Secondary end point(s) |
-The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time
-The incidence of the first case of SARS-CoV-2 RT-PCR positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using CDC criteria
- The incidence of the first case of SARS-CoV-2 RT-PCR positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford defined symptom criteria.
-The incidence of the first case of SARS-CoV-2 RT-PCR positive symptomatic illness occurring ≥ 15 days post second dose of study intervention regardless of evidence of prior SARS-CoV-2 infection
-The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention
-The incidence of COVID-19-related Emergency Department visits occurring ≥ 15 days post second dose of study intervention
-Post-treatment GMTs and GMFRs from day of dosing baseline value to 28 days post each dose in SARS-CoV-2 S, RBD antibodies (MSD serology assay)
- The proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers from day of dosing baseline value to 28 days post each dose) to the S, RBD antigens of AZD1222 (MSD serology assay)
- Post-treatment GMTs and GMFRs from day of dosing baseline value to 28 days post each dose in SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)
-Proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers from day of dosing baseline value to 28 days post each dose) to AZD1222 as measured by SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)≥ 15 days post second dose of study intervention |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints vary for each endpoint. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Chile |
Colombia |
India |
Peru |
United States |
Czechia |
France |
Germany |
Italy |
Netherlands |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |