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

NCT ID: NCT04333732

Last Updated: 2024-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3411 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-04
• Study Completion Date: 2021-12-03

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.

Conditions

COVID 19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

M-M-R II ®

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

Group Type: EXPERIMENTAL

MR or M-M-R II ® vaccine

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo injection

Interventions

MR or M-M-R II ® vaccine

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

Intervention Type: DRUG

Placebo

Placebo injection

Intervention Type: DRUG

Other Intervention Names

Merck

Eligibility Criteria

Inclusion Criteria

1. Volunteers without clinical evidence of COVID-19 infection aged 18 years and older.

2. 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.

3. Must have a mobile phone and access to the Internet for data collection purposes.

4. Participants who are willing and able to provide informed consent via an electronic consent process.

Exclusion Criteria

1. Prior enrollment into other COVID-19 interventional prevention or treatment trials (observational trials not excluded).

2. Self-reported or diagnosed current infection with SARS-CoV-2 or previous COVID-19 diagnosis.

3. Self-reported current acute respiratory infection.

4. 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.

5. Self-reported known allergies to any of the IMPs and excipients of the IMPs and placebo.

6. Self-reported presence or history of the conditions listed in the appendices.

7. Self-reported current use of medication known to interact with any of the medications listed in the appendices.

8. 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

COVID -19 Therapeutics Accelerator

UNKNOWN

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Michael Avidan

Professor of Anesthesiology and Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael S. Avidan, MBBCh

Role: PRINCIPAL_INVESTIGATOR

Washington Univeristy School of Medicine

Ramani Moonesinghe, MD

Role: PRINCIPAL_INVESTIGATOR

University College, London

Helen Rees, MD

Role: PRINCIPAL_INVESTIGATOR

Wits University

Locations

Washington University School of Medicine

St Louis, Missouri, United States

University of Ghana Medical Centre

Accra, Greater Accra Region, Ghana

Groote Schuur/J52, Desmond Tutu Health Foundation

Mowbray, Cape Town, South Africa

Masiphumelele, Desmond Tutu Health Foundation

Sunnydale, Cape Town, South Africa

JOSHA Research

Bloemfontein, Free State, South Africa

Wits RHI, University of the Witwatersrand

Hillbrow, Johannesburg,Gauteng, South Africa

Clinical HIV Research Unit (CHRU)

Auckland Park, Johannesburg, South Africa

Perinatal HIV Research Unit (PHRU)

Diepkloof, Johannesburg, South Africa

Setshaba Research Centre

Soshanguve, Tshwane, South Africa

Groote Schuur Hospital

Cape Town, Western Cape, South Africa

FAMCRU (Family Clinical Research with Ubuntu)

Cape Town, , South Africa

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

Chatsworth, , South Africa

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

Durban, , South Africa

Aurum Institute Tembisa

Tembisa, , South Africa

University College London

London, , United Kingdom

Levy Mwanawasa University Teaching Hospital

Lusaka, , Zambia

Centre for Infectious Disease Research in Zambia [CIDRZ]

Lusaka, , Zambia

Countries

United States; Ghana; South Africa; United Kingdom; Zambia

References

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.

Reference Type: DERIVED

PMID: 41035643 (View on PubMed)

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Reference Type: DERIVED

PMID: 37153751 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35713300 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34473343 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

INV-017499

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

202004099

Identifier Type: -

Identifier Source: org_study_id