COVID 19Phase 3CROWN CORONANCT04333732
CROWN CORONATION: COVID-19 Research Outcomes Worldwide Network for CORONAvirus prevenTION
A Phase 3 study testing MR or M-M-R II ® vaccine in people with COVID 19, run by Washington University School of Medicine at 17 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID 19
- What is being tested?
- MR or M-M-R II ® vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,411 participants
- Where
- 17 sitesin 5 countries
- Study dates
- 4 Sep 2020to 3 Dec 2021
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 22Show fewer
- 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
Trial locations and contacts
17 sites in 5 countries.
17 sites in 5 countries
South Africa12 sites
Clinical HIV Research Unit (CHRU)
Auckland Park, Johannesburg, 2092
JOSHA Research
Bloemfontein, Free State, 9301
Groote Schuur Hospital
Cape Town, Western Cape, 7925
FAMCRU (Family Clinical Research with Ubuntu)
Cape Town, 7505
Chatsworth, HIV Prevention Research Unit, South African Medical Research Council
Chatsworth, 4030
Perinatal HIV Research Unit (PHRU)
Diepkloof, Johannesburg, 1864
Isipingo, HIV Prevention Research Unit, South African Medical Research Council
Durban, 4133
Wits RHI, University of the Witwatersrand
Hillbrow, Johannesburg,Gauteng, 2001
Groote Schuur/J52, Desmond Tutu Health Foundation
Mowbray, Cape Town, 7925
Setshaba Research Centre
Soshanguve, Tshwane, 0152
Masiphumelele, Desmond Tutu Health Foundation
Sunnydale, Cape Town, 7975
Aurum Institute Tembisa
Tembisa, 1632
Zambia2 sites
Levy Mwanawasa University Teaching Hospital
Lusaka, 10101
Centre for Infectious Disease Research in Zambia [CIDRZ]
Lusaka, H8R9+9V
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
Ghana1 site
University of Ghana Medical Centre
Accra, Greater Accra Region, 00233
About this study
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
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.
Read the 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
- Being tested
- MR or M-M-R II ® vaccine, Placebo
- Keywords
- COVID 19, Health care workers, M-M-R II ®
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR or M-M-R II ® vaccineDrug
Also called Merck
Education and surveillance plus MR or M-M-R II ® vaccine
PlaceboDrug
Placebo injection
| Study group | Role | What they receive |
|---|---|---|
| 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 ® Receives: 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 60 days after receiving trial intervention
Secondary outcomes (4)
Number of Participants With Symptomatic COVID-19 at 150 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 150 after receiving trial intervention.
Measured: 150 days after receiving trial intervention
Severity of COVID-19 Measured at 60 Days After Intervention
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). Practically, this outcome measure was treated as a binary outcome - participants were classified and counted as having severe COVID-19 if they met the definition for the primary outcome of symptomatic COVID-19 AND were hospitalized during the course of their COVID-19 illness.
Measured: 60 days after receiving trial intervention
Severity of COVID-19 at 150 Days After Intervention
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). Practically, this outcome measure was treated as a binary outcome - participants were classified and counted as having severe COVID-19 if they met the definition for the primary outcome of symptomatic COVID-19 AND were hospitalized during the course of their COVID-19 illness.
Measured: 150 days
Risk of SARS-CoV-2 Infection up to 150 Days After Trial Intervention
Risk 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. Infection with SARS CoV-2 during the course of the trial was diagnosed when IgG antibodies to the viral nucleocapsid protein were present from the 150 day specimen, but not the baseline specimen.
Measured: 150 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2020
- Study start4 Sep 2020
- Primary completion10 Aug 2021
- Study completion3 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3,411 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- COVID -19 Therapeutics Accelerator
- Responsible party
- Principal investigator, Michael Avidan, Washington University School of Medicine
- Investigators
- Michael S. Avidan, MBBCh, Principal investigator, Washington Univeristy School of MedicineRamani Moonesinghe, MD, Principal investigator, University College, LondonHelen Rees, MD, Principal investigator, Wits University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04333732
- Sponsor's protocol ID
- 202004099
- Other IDs
- INV-017499
- Acronym
- CROWN CORONA
- Status last verified
- Jan 2024
- First submitted
- 31 Mar 2020
- Last updated
- 26 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the main publication may be shared, after de-identification.
Publications
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.
PubMed 41035643Noverr 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.
PubMed 37153751Hirsch 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.
PubMed 35713300Kreuzberger 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.
PubMed 34473343