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

NCT04333732 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 202004099INV-017499
• Study Type: interventional
• Target: 3,411
• Locations: 4 countries
• Sites: 5

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.

Conditions

COVID 19

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Symptomatic COVID-19 at 60 Days

  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.

  60 days after receiving trial intervention

Secondary Outcomes (4)

• Number of Participants With Symptomatic COVID-19 at 150 Days

  150 days after receiving trial intervention

• Severity of COVID-19 Measured at 60 Days After Intervention

  60 days after receiving trial intervention

• Severity of COVID-19 at 150 Days After Intervention

  150 days

• Risk of SARS-CoV-2 Infection up to 150 Days After Trial Intervention

  150 days

Study Arms (2)

M-M-R II ®

EXPERIMENTAL

Education and surveillance plus M-M-R II ® Single dose, 0.5 mL subcutaneous injection of M-M-R II ®

Drug: MR or M-M-R II ® vaccine

Placebo

PLACEBO COMPARATOR

Education and surveillance plus placebo Single dose, 0.5 mL subcutaneous injection of 0.9% saline

Drug: Placebo

Interventions

MR or M-M-R II ® vaccine DRUG

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

Also known as: Merck

M-M-R II ®

Placebo DRUG

Placebo injection

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• COVID -19 Therapeutics Accelerator: collaborator

Study Sites (17)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Ghana Medical Centre

Accra, Greater Accra Region, 00233, Ghana

Location

Groote Schuur/J52, Desmond Tutu Health Foundation

Mowbray, Cape Town, 7925, South Africa

Location

Masiphumelele, Desmond Tutu Health Foundation

Sunnydale, Cape Town, 7975, South Africa

Location

JOSHA Research

Bloemfontein, Free State, 9301, South Africa

Location

Wits RHI, University of the Witwatersrand

Hillbrow, Johannesburg,Gauteng, 2001, South Africa

Location

Clinical HIV Research Unit (CHRU)

Auckland Park, Johannesburg, 2092, South Africa

Location

Perinatal HIV Research Unit (PHRU)

Diepkloof, Johannesburg, 1864, South Africa

Location

Setshaba Research Centre

Soshanguve, Tshwane, 0152, South Africa

Location

Groote Schuur Hospital

Cape Town, Western Cape, 7925, South Africa

Location

FAMCRU (Family Clinical Research with Ubuntu)

Cape Town, 7505, South Africa

Location

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

Chatsworth, 4030, South Africa

Location

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

Durban, 4133, South Africa

Location

Aurum Institute Tembisa

Tembisa, 1632, South Africa

Location

University College London

London, W1W 7TY, United Kingdom

Location

Levy Mwanawasa University Teaching Hospital

Lusaka, 10101, Zambia

Location

Centre for Infectious Disease Research in Zambia [CIDRZ]

Lusaka, H8R9+9V, Zambia

Location

Related Publications (4)

• Delany-Moretlwe S, Dehbi HM, Sikazwe I, Kyei G, Koram K, Dubberke E, Mwelase N, Hague D, Bekker LG, Yun L, Nel A, du Toit L, Biccard B, Gill K, Chipeta C, Mngadi KT, Lebina L, Dassaye R, Asari V, Fry SH, Turton E, Ahmed K, Kusi K, Adu-Amankwah S, Chilengi R, Chilekwa JC, Lovat L, McGuckin D, Caverly E, Politi M, Swan B, DeSchryver A, McKinnon S, Gupta A, Jones G, Freemantle N, Khader S, Rees H, Netea MG, Moonesinghe SR, Avidan MS. No evidence of MMR induced trained immunity to prevent SARS COV2: results from a multi-centre RCT. Front Immunol. 2025 Sep 16;16:1588190. doi: 10.3389/fimmu.2025.1588190. eCollection 2025.

  PMID: 41035643 DERIVED

• Noverr MC, Yano J, Hagensee ME, Lin HY, Meyaski MC, Meyaski E, Cameron J, Shellito J, Trauth A, Fidel PL Jr. Effect of MMR Vaccination to Mitigate Severe Sequelae Associated With COVID-19: Challenges and Lessons Learned. Med Res Arch. 2023 Feb;11(2):3598. doi: 10.18103/mra.v11i2.3598.

  PMID: 37153751 DERIVED

• 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.

  PMID: 35713300 DERIVED

• 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.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Professor Michael S. Avidan
• Organization: Washington University School of Medicine in Saint Louis

avidanm@wustl.edu

+1-(314)-273-2456

Study Officials

• Michael S. Avidan, MBBCh

  Washington Univeristy School of Medicine

  PRINCIPAL INVESTIGATOR

• Ramani Moonesinghe, MD

  University College, London

  PRINCIPAL INVESTIGATOR

• Helen Rees, MD

  Wits University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology and Surgery

Model Details: 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.

Study Record Dates

• First Submitted: March 31, 2020
• First Posted: April 3, 2020
• Study Start: September 4, 2020
• Primary Completion: August 10, 2021
• Study Completion: December 3, 2021
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From 3 months after the last patient last visit onward.
• Access Criteria: Investigators whose proposed use of the data has been approved by a review committee identified for this purpose.

Locations

US (1); ZA (2); GB (1); GH (1)