Plain English Summary
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Admissions to hospital and intensive care units of patients with SARS-CoV-2 pneumonia are increasing rapidly. In the UK, the mortality amongst hospital admissions is around 5.2% with case rates doubling every 2-3 days. The death rate following Intensive Care Unit (ICU) admission is currently about 50%. There is currently no vaccine or proven effective treatments for COVID-19 infection.
As COVID-19 is a new illness, we are constantly learning more about how it affects the human body. We know that the COVID-19 virus affects a number of different cells in your body, including a type of blood cell called a macrophage (immune cell), and that it can cause the number of these cells to increase in your body. To fight an infection, your immune cells produce proteins called cytokines and chemokines. These proteins can cause inflammation and at high levels can lead to damage in the tissues and organs in your body. Researchers believe this is why some people with COVID-19 infection become very ill.
This trial plans to look at a number of different potential treatments for patients with COVID-19. The first treatment that will be looked at is called Mylotarg. This drug is routinely used to treat a certain type of blood cancer and could be used to reduce the increased levels of inflammatory cells inside the body. Once this inflammation has been reduced, it may be possible that the immune system will adapt and fight off the virus more effectively.
If this treatment benefits people with COVID-19 in this trial, the drug will be included in another larger-scale clinical trial being conducted throughout the UK, which is designed to compare treatments to find out which is the best at treating this infection.
Who can participate?
Hospitalized adult patients with a laboratory-confirmed diagnosis of COVID-19
What does the study involve?
In this trial, participants will be randomly allocated to receive either usual care only, or usual care and an active treatment. The first treatment will be looked at is called Mylotarg, which will be given through a drip into a vein in the participant’s arm on up to three separate occasions: on Day 1, Day 5, and Day 10 of the trial. The participant may not receive all three doses if they have recovered or they develop side effects and their trial doctor decides that they should not have further doses. Participants will be actively monitored for 28 days as a part of the trial in addition to the standard medical treatment that they will receive.
What are the possible benefits and risks of participating?
If the patient is allocated to receive usual care only, the patient will receive the same medical care as all other patients being treated for COVID-19, this is known as the 'usual care' arm of the trial and carries no additional risks.
If the patient is allocated to receive usual care and an active treatment in the trial (known as the 'usual care' arm of the trial) they will receive the treatment in addition to the usual medical care received by patients who have COVID-19. Patients may have side effects from the treatment whilst taking part in the trial. The trial is testing new ways of treating COVID-19. Although the drug being tested, Mylotarg, is used routinely in the treatment of a type of blood cancer, where there is a lot known about the side effects, it has not been used in the treatment of patients with COVID-19. It is possible that the side effects may be different when used to treat this disease. Everyone taking part in the trial will be monitored carefully for side effects. However, the doctors don’t know all the side effects that may occur.
Mylotarg has not been used to treat patients with respiratory conditions before and we don’t know how it will interact with the other drugs being used to treat COVID-19. Side effects may be mild or serious or may even be life-threatening. The first patients to receive Mylotarg in this trial will be patients who are being treated in the ICU – as we can monitor them very closely for any side effects during and after the infusion. Your doctors may give you medicines to help lessen side effects or the trial treatment may be postponed or stopped, depending on the side-effects you may experience.
Where is the study run from?
University Hospitals Birmingham NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
From March 2020 to May 2021
Who is funding the study?
UK Research and Innovation (UK)
Who is the main contact?
Dr Anna Rowe, firstname.lastname@example.org
Dr Anna Rowe
Cancer Research UK Clinical Trials Unit
University of Birmingham
RG_20-030, CPMS 45648, IRAS 282431
A randomised phase II proof of principle multi-arm multi-stage trial designed to guide the selection of interventions for phase III trials in hospitalised patients with COVID-19 infection.
To investigate potential agents in an early phase trial setting that elicit a change in the ration of oxygen saturation to fractional inspired oxygen concentration in COVID-19 patients
Approved 08/05/2020, East Midlands – Nottingham 2 (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS, UK; +44 (0)207 104 8035 or +44 (0)207 104 8103; email@example.com), ref: 20/EM/0115
Open-label phase II multi-arm multi-stage randomized controlled trial
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format.
COVID-19 (SARS-CoV-2 infection) in hospitalised patients
Randomisation will be performed according to a 1:1 ratio (Usual Care/Control Arm vs. Research Arms). Patients will be randomised using an online randomisation system, using stratification (variable of care status, either on ward or ICU) via minimisation, where relevant to the research arms.
Initial approval was received for a single centre trial, but an amendment is underway to make this a multi-centre trial.
Patients will be randomised into either a control group, or to receive an interventional treatment.
Arm 1: Usual Care (Control)
Arm 2: Usual Care + Gemtuzumab Ozogamicin
Gemtuzumab Ozogamicin will be given intravenously into the arm on up to three separate occasions: on Day 1, Day 5 and Day 10 of the trial. The patient may not receive all three doses if they have recovered or they develop side effects and their trial doctor decides that they should not have any more. Participants will be actively followed up for 28 days from the first dose.
Please Note: Additional intervention arms will be added during the trial via substantial amendment to the protocol
Gemtuzumab ozogamicin (Mylotarg)
Primary outcome measure
The ratio of the oxygen saturation to fractional inspired oxygen concentration (SpO2/FiO2), calculated using SpO2 and FiO2 (or inspired oxygen) measurements taken as part of routine clinical care at least 4-hourly in intensive care, and 4- to 6-hourly on the wards for patients receiving active management. The ratio will be derived from these data from the electronic patient record from baseline (randomisation) to day 14, hospital discharge or death
Secondary outcome measures
These will be aligned with COMET core outcome set initiatives.
1. Efficacy measured by:
1.1. Time to improvement at randomisation to day 7, 14 and 28. Improvement is defined as at least a two-point improvement on the WHO R&D Blueprint Group Clinical Progression improvement Scale (1-10 scale; for the purposes of this trial level 0, no viral RNA detected, will not be assessed).
1.2. WHO R&D Blueprint Group Clinical Progression Scale at randomisation to day 7, 14 and 28.
2. Patient status measured by:
2.1. Respiratory rate taken as part of routine clinical care 4-6 hourly from baseline (randomisation) to day 14, hospital discharge or death
2.2. Body temperature taken as part of routine clinical care at 4-6 hourly from baseline (randomisation) to day 14, hospital discharge or death
2.3. Length of hospital stay from the electronic patient record at hospital discharge or death
2.4. Hospital survival status at day 28
2.5. Proportion of patients discharged at day 28
2.6. Destination of discharge from the electronic patient record at hospital discharge or death
2.7. Routine laboratory measurement of C-reactive protein (CRP), Full blood count with neutrophil:lymphocyte ratios, Ferritin, D-Dimer, LDH and triglycerides at baseline, 1, 3, 7 and 14 days.
3. Safety measured by:
3.1. Adverse events (AEs) as recorded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03 (Appendix 1) of grade ≥3 with interest in veno-occlusive disease, secondary infection and allergic reaction in the event of an AE
3.2. Survival status at day 28, hospital discharge or death
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Hospitalized patients with a laboratory-confirmed diagnosis of SARS-CoV-2 pneumonia (confirmed by reverse transcription polymerase chain reaction [RT-PCR] assay and chest X-ray)
2. Aged ≥16 years
3. Oxygen saturation (SaO2) of ≤94% while breathing ambient air or a ratio of the partial pressure of Oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (PaO2:FiO2) ≤300 mgHg (≤40kPa)
4. Participants recruited up until 3 patients are included in Arm 2 (usual care + gemtuzumab ozogamicin) must be intubated and requiring mechanical ventilation
Target number of participants
This is a platform trial, and is anticipated to have up to 14 interventional arms. These will all open at different times, and arms may close following an interim analysis before reaching the recruitment target of 42 patients per arm.
Participant exclusion criteria
1. Patient or legal representative refusal
2. Receiving palliative care with no active treatment
3. Known veno-occlusive disease
4. Chronic Obstructive Pulmonary Disease (known FEV1 <50% predicted or ambulatory or long term oxygen therapy)
5. Neutrophil count <2 x10⁹ /l or White Blood Cell Count <4.0 x10⁹ /l
6. Current participation in another COVID-19 interventional trial
7. Pregnancy or breastfeeding
8. Women of childbearing potential who are unwilling to use two forms of effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the trial and up to 7 months after the trial drug is administered. If using hormonal agents the same method must have been used for at least one month before the trial dosing and patients must use a barrier method during that time period.
9. Non-vasectomised men, sexually active with women of childbearing potential, who are not willing to practise effective contraception (i.e. condom with spermicide) for the duration of the trial and up to 4 months after the trial drug is administered
10. Known HIV or chronic Hepatitis B or C infection
11. Known contraindications to any of the Investigational Medicinal Products (IMPs)
12. Concurrent immunosuppression with biological agents or prednisone dose >20mg
13. History of hematopoietic stem cell transplant or solid organ transplant
14. Any other indication or medical history, that in the opinion of the local investigator means the patient is unsuitable for trial participation
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
University Hospitals Birmingham NHS Foundation Trust
Mindelsohn Way Edgbaston
UK Research and Innovation
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
A Lay Summary of the findings will be produced after the completion of all analysis and made available to all patients via trial websites. The Lay Summary will be produced by the Sponsor and reviewed by a PPI panel. At the end of the trial, the findings will be published in peer-reviewed medical and scientific journals. These publications will be available upon request from the patient’s trial doctor.
Results will also be disseminated at internal meetings, conferences, trial web site and peer-reviewed scientific journals.
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)