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CROWN CORONATION: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION (CROWN CORONA)

Primary Purpose

COVID 19

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

MR or M-M-R II ® vaccine

Placebo

About this trial

This is an interventional prevention trial for COVID 19 focused on measuring COVID 19, Health care workers, M-M-R II ®

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

Volunteers without clinical evidence of COVID-19 infection aged 18 years and older.
Healthcare workers based in a primary, secondary or tertiary healthcare setting with a high risk of developing COVID-19 due to their potential exposure to patients with SARS-CoV-2 infection.
Must have a mobile phone and access to the Internet for data collection purposes.
Participants who are willing and able to provide informed consent via an electronic consent process.

Exclusion criteria

Prior enrollment into other COVID-19 interventional prevention or treatment trials (observational trials not excluded).
Self-reported or diagnosed current infection with SARS-CoV-2 or previous COVID-19 diagnosis.
Self-reported current acute respiratory infection.
Concurrent and/or recent involvement in other research or use of the investigational product, a product considered to be equivalent to the investigational product, or any other product that is likely to interfere with the investigational products in this trial used within three months of study enrolment.
Self-reported known allergies to any of the IMPs and excipients of the IMPs and placebo.
Self-reported presence or history of the conditions listed in the appendices.
Self-reported current use of medication known to interact with any of the medications listed in the appendices.
Inability or unwillingness to be followed up for the trial period.

For M-M-R II

Pregnant women.
Individuals receiving high dose corticosteroids, other immuno-suppressive drugs, alkylating agents or anti-metabolites.
Individuals undergoing radiotherapy.
Any malignant disease either untreated or currently undergoing therapy.
History of administration of gammaglobulin or blood transfusions within the previous 3 months.
Participants with an allergy to the MR (MMR) vaccine or its components, including neomycin.
Idiopathic thrombocytopenic purpura (ITP)
Untreated tuberculosis
Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrollment
Planned receipt of any vaccine other than the study intervention within 30 days before and after the study vaccination (not including the flu vaccination via injection)
Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).
Any confirmed or suspected immunosuppressive or immunodeficient state, including untreated HIV infection with a CD4T count <200 /mL
Asplenia

Sites / Locations

Washington University School of Medicine
University of Ghana Medical Centre
Groote Schuur/J52, Desmond Tutu Health Foundation
Masiphumelele, Desmond Tutu Health Foundation
JOSHA Research
Wits RHI, University of the Witwatersrand
Clinical HIV Research Unit (CHRU)
Perinatal HIV Research Unit (PHRU)
Setshaba Research Centre
Groote Schuur Hospital
FAMCRU (Family Clinical Research with Ubuntu)
Chatsworth, HIV Prevention Research Unit, South African Medical Research Council
Isipingo, HIV Prevention Research Unit, South African Medical Research Council
Aurum Institute Tembisa
University College London
Levy Mwanawasa University Teaching Hospital
Centre for Infectious Disease Research in Zambia [CIDRZ]

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

M-M-R II ®

Placebo

Arm Description

Education and surveillance plus M-M-R II ®

Education and surveillance plus placebo

Outcomes

Primary Outcome Measures

Symptomatic COVID-19

Incidence of symptomatic (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, nausea, vomiting, or diarrhea), laboratory test-confirmed COVID-19 in the intervention and control groups in adults with repeated exposures to SARS-CoV-2 by day 60 after receiving trial intervention.

Secondary Outcome Measures

Symptomatic COVID-19

Severity of COVID-19

Severity of COVID-19 in adults who become infected with SARS-CoV-2 by day 60 after receiving trial intervention. Severity will be graded on a simplified version of the ordinal WHO COVID-19 severity scale ((i) uninfected, (ii) infected but ambulatory [mild disease], (iii) infected and hospitalized [moderate or severe disease] or dead).

Severity of COVID-19

Severity of COVID-19 in adults who become infected with SARS-CoV-2 by day 150 after receiving trial intervention. Severity will be graded on a simplified version of the ordinal WHO COVID-19 severity scale ((i) uninfected, (ii) infected but ambulatory [mild disease], (iii) infected and hospitalized [moderate or severe disease] or dead).

SARS-CoV-2 infection

Incidence of SARS-CoV-2 infection by serology (anti-nucleocapsid antibody) in the intervention and control groups in adults with repeated exposures to SARS-CoV-2 by day 150 after receiving trial intervention.

Full Information

NCT ID

NCT04333732

First Posted

March 31, 2020

Last Updated

January 25, 2022

Sponsor

Washington University School of Medicine

Collaborators

COVID -19 Therapeutics Accelerator

1. Study Identification

Unique Protocol Identification Number

NCT04333732

Brief Title

CROWN CORONATION: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION

Acronym

CROWN CORONA

Official Title

An International, Multi-site, Bayesian Platform Adaptive, Randomized, Placebo-controlled Trial Assessing the Effectiveness of Candidate Agents in Mitigating COVID-19 Disease in Adults

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

September 4, 2020 (Actual)

Primary Completion Date

August 10, 2021 (Actual)

Study Completion Date

December 3, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Washington University School of Medicine

Collaborators

COVID -19 Therapeutics Accelerator

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The objective of CROWN CORONATION is the prevention of symptomatic COVID-19 by using combinations of approved and safe repurposed interventions, with complementary mechanisms of action.

Detailed Description

CROWN CORONATION is an international, Bayesian platform adaptive, randomized, placebo-controlled trial assessing the effectiveness of candidate interventions in preventing COVID-19 disease in adults. Randomization will be stratified by age (<50 and ≥50) and site. Participants will be healthcare workers at risk of contracting SARS-CoV-2. Participants will be randomized into one of two arms: Education and surveillance plus MR or MMR vaccine Education and surveillance plus Placebo While the initial intervention to be tested on the platform will be the MR or MMR vaccine, other interventions might be added or removed over the course of the trial. The trial will evaluate which of the intervention arms is most effective at decreasing the incidence of symptomatic COVID-19 disease, without unacceptable side effects or safety events. All participants will require be required to have a mobile phone to participate. This is standard in all the countries in this study. Most, but not all, will also have a smartphone. Participants will complete weekly data logs via SMS texting. Follow-up information will be collected until approximately 5 months after the end of treatment or death. Participants who develop symptomatic COVID-19 during the last month of observation will at a minimum be followed-up until symptom resolution and at a maximum until 6 months after randomization (whichever comes first). Telemedicine approaches to collecting information on participants will be used where possible. The trial will provide adherence support interventions that have been shown in randomized controlled trials to improve adherence to Human Immunodeficiency Virus treatment and adapted for HIV Pre-Exposure Prophylaxis (HIV PrEP) (e.g. two-way SMS with check in for those that report symptoms or adverse events). The database will be hosted on UK-based servers which are expected to be managed by Sealed Envelope Ltd. Local investigators will have access to the part of the CRF to enable recording of outcome data and/or severity of COVID-19 symptoms. Participants will be given a secure login to enable them to complete an initial participant health questionnaire and the regular data logs. It is envisaged that these will be completed at least weekly.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID 19

Keywords

COVID 19, Health care workers, M-M-R II ®

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

An international, multi-site, randomized, placebo-controlled, Bayesian platform clinical trial. Initially there will be 2 arms, but we anticipate adding intervention arms to the platform. Combining interventions, allowing assessment of potential interactions, will be considered when arms are added.

Masking

ParticipantInvestigator

Masking Description

For the MR or MMR vaccine, there will be a placebo vaccine. Attempts will be made to maintain masking for other interventions (e.g. oral tablets) added to the platform by including suitable placebo options.

Allocation

Randomized

Enrollment

3545 (Actual)

8. Arms, Groups, and Interventions

Arm Title

M-M-R II ®

Arm Type

Experimental

Arm Description

Education and surveillance plus M-M-R II ®

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Education and surveillance plus placebo

Intervention Type

Drug

Intervention Name(s)

MR or M-M-R II ® vaccine

Other Intervention Name(s)

Merck

Intervention Description

Education and surveillance plus MR or M-M-R II ® vaccine

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo injection

Primary Outcome Measure Information:

Title

Symptomatic COVID-19

Description

Time Frame

60 days after receiving trial intervention

Secondary Outcome Measure Information:

Title

Symptomatic COVID-19

Description

Time Frame

150 days after receiving trial intervention

Title

Severity of COVID-19

Description

Time Frame

60 days after receiving trial intervention

Title

Severity of COVID-19

Description

Time Frame

150 days

Title

SARS-CoV-2 infection

Description

Time Frame

150 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria Volunteers without clinical evidence of COVID-19 infection aged 18 years and older. Healthcare workers based in a primary, secondary or tertiary healthcare setting with a high risk of developing COVID-19 due to their potential exposure to patients with SARS-CoV-2 infection. Must have a mobile phone and access to the Internet for data collection purposes. Participants who are willing and able to provide informed consent via an electronic consent process. Exclusion criteria Prior enrollment into other COVID-19 interventional prevention or treatment trials (observational trials not excluded). Self-reported or diagnosed current infection with SARS-CoV-2 or previous COVID-19 diagnosis. Self-reported current acute respiratory infection. Concurrent and/or recent involvement in other research or use of the investigational product, a product considered to be equivalent to the investigational product, or any other product that is likely to interfere with the investigational products in this trial used within three months of study enrolment. Self-reported known allergies to any of the IMPs and excipients of the IMPs and placebo. Self-reported presence or history of the conditions listed in the appendices. Self-reported current use of medication known to interact with any of the medications listed in the appendices. Inability or unwillingness to be followed up for the trial period. For M-M-R II Pregnant women. Individuals receiving high dose corticosteroids, other immuno-suppressive drugs, alkylating agents or anti-metabolites. Individuals undergoing radiotherapy. Any malignant disease either untreated or currently undergoing therapy. History of administration of gammaglobulin or blood transfusions within the previous 3 months. Participants with an allergy to the MR (MMR) vaccine or its components, including neomycin. Idiopathic thrombocytopenic purpura (ITP) Untreated tuberculosis Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrollment Planned receipt of any vaccine other than the study intervention within 30 days before and after the study vaccination (not including the flu vaccination via injection) Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). Any confirmed or suspected immunosuppressive or immunodeficient state, including untreated HIV infection with a CD4T count <200 /mL Asplenia

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael S. Avidan, MBBCh

Organizational Affiliation

Washington Univeristy School of Medicine

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ramani Moonesinghe, MD

Organizational Affiliation

University College, London

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Helen Rees, MD

Organizational Affiliation

Wits University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

University of Ghana Medical Centre

City

Accra

State/Province

Greater Accra Region

ZIP/Postal Code

00233

Country

Ghana

Facility Name

Groote Schuur/J52, Desmond Tutu Health Foundation

City

Mowbray

State/Province

Cape Town

ZIP/Postal Code

7925

Country

South Africa

Facility Name

Masiphumelele, Desmond Tutu Health Foundation

City

Sunnydale

State/Province

Cape Town

ZIP/Postal Code

7975

Country

South Africa

Facility Name

JOSHA Research

City

Bloemfontein

State/Province

Free State

ZIP/Postal Code

9301

Country

South Africa

Facility Name

Wits RHI, University of the Witwatersrand

City

Hillbrow

State/Province

Johannesburg,Gauteng

ZIP/Postal Code

2001

Country

South Africa

Facility Name

Clinical HIV Research Unit (CHRU)

City

Auckland Park

State/Province

Johannesburg

ZIP/Postal Code

2092

Country

South Africa

Facility Name

Perinatal HIV Research Unit (PHRU)

City

Diepkloof

State/Province

Johannesburg

ZIP/Postal Code

1864

Country

South Africa

Facility Name

Setshaba Research Centre

City

Soshanguve

State/Province

Tshwane

ZIP/Postal Code

0152

Country

South Africa

Facility Name

Groote Schuur Hospital

City

Cape Town

State/Province

Western Cape

ZIP/Postal Code

7925

Country

South Africa

Facility Name

FAMCRU (Family Clinical Research with Ubuntu)

City

Cape Town

ZIP/Postal Code

7505

Country

South Africa

Facility Name

Chatsworth, HIV Prevention Research Unit, South African Medical Research Council

City

Chatsworth

ZIP/Postal Code

4030

Country

South Africa

Facility Name

Isipingo, HIV Prevention Research Unit, South African Medical Research Council

City

Durban

ZIP/Postal Code

4133

Country

South Africa

Facility Name

Aurum Institute Tembisa

City

Tembisa

ZIP/Postal Code

1632

Country

South Africa

Facility Name

University College London

City

London

ZIP/Postal Code

W1W 7TY

Country

United Kingdom

Facility Name

Levy Mwanawasa University Teaching Hospital

City

Lusaka

ZIP/Postal Code

10101

Country

Zambia

Facility Name

Centre for Infectious Disease Research in Zambia [CIDRZ]

City

Lusaka

ZIP/Postal Code

H8R9+9V

Country

Zambia

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant data that underlie the results reported in the main publication may be shared, after de-identification.

IPD Sharing Time Frame

From 3 months after the last patient last visit onward.

IPD Sharing Access Criteria

Investigators whose proposed use of the data has been approved by a review committee identified for this purpose.

Citations:

PubMed Identifier

35713300

Citation

Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.

Results Reference

derived

PubMed Identifier

34473343

Citation

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Results Reference

derived

Learn more about this trial

CROWN CORONATION: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION

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