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Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04516746
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : November 13, 2020
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 17, 2020
First Posted Date  ICMJE August 18, 2020
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE August 28, 2020
Estimated Primary Completion Date December 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 29, 2020)
  • The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age [ Time Frame: 1 year ]
    A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case.
  • The safety and tolerability of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age [ Time Frame: a: 28 days post each dose of study Intervention. / b: from Day 1 post-treatment through Day 730. ]
    1. Incidence of adverse events.
    2. Incidence of serious adverse events, medically attended adverse events, and adverse events of special interest.
  • The reactogenicity of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age (Substudy only) [ Time Frame: 7 days post each dose of study intervention. ]
    Incidence of local and systemic solicited adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: August 17, 2020)
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age [ Time Frame: 1 year ]
    A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case.
  • To assess the safety and tolerability of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age [ Time Frame: a: 28 days post each dose of study Intervention. / b: from Day 1 post-treatment through Day 730. ]
    1. Incidence of adverse events.
    2. Incidence of serious adverse events, medically attended adverse events, and adverse events of special interest.
  • To assess the reactogenicity of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age (Substudy only) [ Time Frame: 7 days post each dose of study intervention. ]
    Incidence of local and systemic solicited adverse events.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2020)
  • The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection [ Time Frame: 1 year ]
    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 efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of symptomatic COVID-19 using CDC criteria [ Time Frame: 1 year ]
    The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness for a participant occurring at or after 15 days post second dose of study intervention using criteria from the CDC.
  • The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of University of Oxford defined symptomatic COVID-19 [ Time Frame: 1 year ]
    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 efficacy of 2 IM doses of AZD12222 compared to placebo for the prevention of severe or critical symptomatic COVID-19. [ Time Frame: 1 year ]
    The incidence of SARS-CoV-RT-PCR-positive severe or critical symptomatic illness occurring 15 days or more post second dose of study intervention.
  • The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19-related Emergency Department visits [ Time Frame: 1 year ]
    The incidence of COVID-19-related Emergency Department visits occurring ≥ 15 days post second dose of study intervention
  • Antibody responses to AZD1222 S antigen following 2 IM doses of AZD1222 or placebo (Substudy and Illness Visits only) [ Time Frame: 28 days post each dose ]
    Post-treatment GMTs and GMFRs 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) to the S, RBD antigens of AZD1222 (MSD serology assay)
  • Anti-SARS-CoV-2 neutralizing antibody levels in serum following 2 IM doses of AZD1222 or placebo (Sub-study and Illness Visits only) [ Time Frame: 28 days post each dose ]
    Post-treatment GMTs and GMFRs 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) to AZD1222 as measured by SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)
Original Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2020)
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 asymptomatic infection [ Time Frame: 1 year ]
    Proportion of participants positive for SARS-CoV-2 Nucleocapsid antibodies over time.
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of symptomatic COVID-19 using CDC criteria [ Time Frame: 1 year ]
    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
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of University of Oxford defined symptomatic COVID-19 [ Time Frame: 1 year ]
    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
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of severe or critical symptomatic COVID-19 [ Time Frame: 1 year ]
    The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring ≥ 15 days post second dose of study intervention.
  • To estimate the efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19-related Emergency Department visits [ Time Frame: 1 year ]
    The incidence of COVID-19-related Emergency Department visits occurring ≥ 15 days post second dose of study intervention
  • To assess antibody responses to AZD1222 S antigen following 2 IM doses of AZD1222 or placebo (Substudy and Illness Visits only) [ Time Frame: 28 days post each dose ]
    Post-treatment GMTs and GMFRs 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) to the S, RBD antigens of AZD1222 (MSD serology assay)
  • To determine anti-SARS-CoV-2 neutralizing antibody levels in serum following 2 IM doses of AZD1222 or placebo (Sub-study and Illness Visits only) [ Time Frame: 28 days post each dose ]
    Post-treatment GMTs and GMFRs 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) to AZD1222 as measured by SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Double-blind, Placebo-controlled Study of AZD1222 for the Prevention of COVID-19 in Adults
Official Title  ICMJE A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19
Brief Summary The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.
Detailed Description The COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. Currently, there are no specific treatments available against COVID-19 and accelerated vaccine development is urgently needed. A safe and effective vaccine for COVID-19 prevention would have significant public health impact.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Participants are assigned to one of two or more groups in parallel for the duration of the study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind: two or more parties are unaware of the intervention assignment.
Primary Purpose: Treatment
Condition  ICMJE
  • COVID-19
  • SARS-CoV-2
Intervention  ICMJE
  • Biological: AZD1222
    AZD12222 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2-5 surface glycoprotein.
  • Biological: Placebo
    Commercially available 0.9% (n/V) saline for injection.
Study Arms  ICMJE
  • Experimental: AZD1222
    2 IM doses of 5 × 10^10 vp (nominal, ± 1.5 × 10^10 vp) AZD1222 4 weeks apart
    Intervention: Biological: AZD1222
  • Placebo Comparator: Placebo
    2 IM doses of saline placebo 4 weeks apart
    Intervention: Biological: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2020)
40051
Original Estimated Enrollment  ICMJE
 (submitted: August 17, 2020)
30000
Estimated Study Completion Date  ICMJE October 25, 2022
Estimated Primary Completion Date December 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Increased risk of SARS-CoV-2 infection
  • Medically stable

Exclusion Criteria:

  • confirmed or suspected immunosuppressive or immunodeficient state
  • significant disease, disorder, or finding
  • Prior or concomitant vaccine therapy for COVID-19
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Chile,   Colombia,   Peru,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04516746
Other Study ID Numbers  ICMJE D8110C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
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
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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Iqvia Pty Ltd
Investigators  ICMJE
Principal Investigator: Ann Falsey, MD University of Rochester
Principal Investigator: Magda Sobieszczyk, MD Columbia University
PRS Account AstraZeneca
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP