Which treatment could lessen the severity of a coronavirus infection when compared with usual care in an NHS setting?
| ISRCTN | ISRCTN40580903 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN40580903 |
| EudraCT/CTIS number | 2020-001684-85 |
| IRAS number | 282431 |
| Secondary identifying numbers | RG_20-030, CPMS 45648, IRAS 282431 |
- Submission date
- 14/05/2020
- Registration date
- 15/05/2020
- Last edited
- 30/08/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Respiratory
Plain English summary of protocol
Current plain English summary as of 01/07/2020:
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. A new, unlicensed drug called namilumab which has been tested in patients with arthritis and other inflammatory conditions may reduce inflammation in the body caused by the coronavirus. It is currently being given to patients with COVID-19 in a clinical trial in Italy. Namilumab is being provided free of charge by Izana Bioscience Limited for use in this trial.
A drug called infliximab (Remsima) which is widely used to treat arthritis and other conditions may reduce inflammation in the body caused by the coronavirus. Infliximab is being provided free of charge by Celltrion Healthcare UK Limited for use in this trial.
A drug called Mylotarg 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. NOTE: This treatment arm is not currently open to recruitment.
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?
Hospitalised 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. As well as the usual care group, there are currently three active treatment groups; Mylotarg, namilumab and infliximab. NOTE: The Mylotarg group is not open to recruitment at present. Namilumab and infliximab will be given through a drip into a vein in the participant’s arm as a single dose on Day 1 of the trial. 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' group) 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, namilumab and infliximab have 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.
Namilumab is currently being used on compassionate grounds for COVID-19 patients in Italy, however this is still an unlicensed drug and more information is needed.
Side effects of any of the trial drugs may be mild or serious or may even be life-threatening.
T he first patients to receive Mylotarg treatment in this trial will be patients who are being treated in the ICU as they can be monitored very closely for any side effects during and after the infusion. Patients recruited to namilumab and infliximab arms can be recruited from and treated on the ward. The doctors may give participants medicines to help lessen side effects or the trial treatment may be postponed or stopped, depending on the side effects they 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?
March 2020 to May 2021
Who is funding the study?
UK Research and Innovation (UK)
Who is the main contact?
Dr Anna Rowe
catalyst@trials.bham.ac.uk
______
Previous plain English summary as of 30/06/2020:
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. A new, unlicensed drug called namilumab which has been tested in patients with arthritis and other inflammatory conditions may reduce inflammation in the body caused by the coronavirus. It is currently being given to patients with COVID-19 in a clinical trial in Italy. Namilumab is being provided free of charge by Izana Bioscience Limited for use in this trial.
A drug called infliximab (Remsima) which is widely used to treat arthritis and other conditions may reduce inflammation in the body caused by the coronavirus. Infliximab is being provided free of charge by Celltrion Healthcare UK Limited for use in this trial.
A drug called Mylotarg 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. NOTE: This treatment arm is not currently open to recruitment.
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. As well as the usual care group, there are currently three active treatment groups; Mylotarg, namilumab and infliximab. NOTE: The Mylotarg group is not open to recruitment at present. Namilumab and infliximab will be given through a drip into a vein in the participant’s arm as a single dose on Day 1 of the trial. 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' group) 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, namilumab and infliximab have 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 treatment in this trial will be patients who are being treated in the ICU as they can be monitored very closely for any side effects during and after the infusion. The doctors may give participants medicines to help lessen side effects or the trial treatment may be postponed or stopped, depending on the side effects they 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?
March 2020 to May 2021
Who is funding the study?
UK Research and Innovation (UK)
Who is the main contact?
Dr Anna Rowe
catalyst@trials.bham.ac.uk
______
Previous 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, catalyst@trials.bham.ac.uk
Contact information
Public
Cancer Research UK Clinical Trials Unit
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| catalyst@trials.bham.ac.uk |
Study information
| Study design | Open-label phase II multi-arm multi-stage randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format. |
| Scientific title | 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. |
| Study acronym | CATALYST |
| Study objectives | 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 |
| Ethics approval(s) | 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; nottingham2.rec@hra.nhs.uk), ref: 20/EM/0115 |
| Health condition(s) or problem(s) studied | COVID-19 (SARS-CoV-2 infection) in hospitalised patients |
| Intervention | Current interventions as of 01/07/2020: 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 - THIS ARMS IS NOT CURRENTLY OPEN TO RECRUITMENT Arm 3: Usual Care + Namilumab Arm 4: Usual Care + Infliximab Arm 2: 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 last dose. - THIS ARM IS NOT CURRENTLY OPEN TO RECRUITMENT Arm 3: Namilumab will be given will be given intravenously into the arm on Day 1. Participants will be actively followed up for 28 days from the last dose. Arm 4: Infliximab will be given will be given intravenously into the arm on Day 1. Participants will be actively followed up for 28 days from the last dose. Please Note: Additional intervention arms will be added during the trial via substantial amendment to the protocol Previous interventions: 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 |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Gemtuzumab ozogamicin (Mylotarg), Namilumab, Infliximab (Remsima) |
| Primary outcome measure | Current primary outcome measure approved from 12/10/2020, updated 27/08/2021: C-reactive protein levels measured by routine laboratory measurement from baseline and throughout a patients time on the trial (Day 1 through to a maximum of Day 28) Previous 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 | Current secondary outcome measures approved from 12/10/2020, updated 27/08/2021: These will be aligned with COMET core outcome set initiatives and assessed from baseline up to a maximum of Day 28: 1. Efficacy measured by: 1.1 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). 2. Patient status measured by: 2.1. 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 2.2 Respiratory rate taken as part of routine clinical care 4-6 hourly 2.3. Body temperature taken as part of routine clinical care at 4-6 hourly 2.4. Length of hospital stay from the electronic patient record at hospital discharge or death 2.5. Hospital survival status at Day 28 or number of hospital free days 2.6. Proportion of patients discharged at Day 28 2.6. Destination of discharge from the electronic patient record at hospital discharge or death 3. Routine laboratory measurement (from baseline up to a maximum of Day 28) of: 3.1 C-reactive protein (CRP) 3.2 Lymphocyte count, neutrophil count 3.3 Neutrophil:lymphocyte ratios 3.4 Ferritin, D-dimer and LDH 4. Safety measured by: 4.1. 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 4.2. Overall survival Previous 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 study start date | 26/03/2020 |
| Completion date | 01/05/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| 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. |
| Total final enrolment | 146 |
| Key inclusion criteria | Current inclusion criteria approved from 12/10/2020, updated 27/08/2021: 1. Hospitalised adult (≥16 yrs) patients with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription polymerase chain reaction [RT-PCR] assay) 2. CRP ≥40 mg/l Arm 2: (Usual Care + Gemtuzumab Ozogamicin) Specific Inclusion Criteria (NB. THIS ARM IS NOT RECRUITING AT THIS TIME) The following criterion will apply until at least three patients have been allocated the IMP: intubated and requiring mechanical ventilation Previous inclusion criteria from 01/07/2020: 1. Hospitalised adult (≥16 yrs) patients with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription polymerase chain reaction [RT-PCR] assay) 2. 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 mg Hg (≤40kPa) Arm 2: (Usual Care + Gemtuzumab Ozogamicin) Specific Inclusion Criteria (NB. THIS ARM IS NOT RECRUITING AT THIS TIME) The following criterion will apply until at least 3 patients have been allocated the IMP: intubated and requiring mechanical ventilation Original 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 |
| Key exclusion criteria | Current exclusion criteria approved from 12/10/2020, updated 27/08/2021: 1. Patient or legal representative refusal 2. Receiving palliative care with no active treatment 3. Current participation in another COVID-19 interventional trial. Co-enrolment into RECOVERY-RS is allowed 4. Known pregnancy or breastfeeding women 5. Women of child bearing potential who are unwilling to use effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the trial and the maximum period specified in Table 2. 6. 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 the maximum period specified in Table 2. 7. Known HIV or chronic Hepatitis B or C infection 8. Known contraindications to any of the Investigational Medicinal Products (IMPs) 9. Concurrent immunosuppression with biological agents 10. History of haematopoietic stem cell transplant or solid organ transplant 11. Known hypersensitivity to drug products or excipients 12. Patients with tuberculosis or other severe infections such as (non-COVID-19) sepsis, abscesses, and opportunistic infections requiring treatment 13. Patients with moderate or severe heart failure (NYHA class III/IV) 14. Any other indication or medical history, that in the opinion of the local investigator means the patient is unsuitable for trial participation Previous exclusion criteria from 01/07/2020: 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 x 109/l or White Blood Cell Count < 4.0 x 109/l 6. Current participation in another COVID-19 interventional trial. Co-enrolment into 7. RECOVERY-RS is allowed 8. Known pregnancy or breastfeeding women 9. Women of child bearing potential who are unwilling to use effective contraception (i.e. barrier, oral contraceptive pill, implanted contraception, or previous hysterectomy, bilateral oophorectomy) for the duration of the trial and the maximum period specified below. 10. Non-vasectomised men, sexually active with women of child bearing potential, who are not willing to practise effective contraception (i.e. condom with spermicide) for the duration of the trial and the maximum period specified below. 11. Known HIV or chronic Hepatitis B or C infection 12. Known contraindications to any of the Investigational Medicinal Products (IMPs) 13. Concurrent immunosuppression with biological agents 14. History of haematopoietic stem cell transplant or solid organ transplant 15. Known hypersensitivity to drug products or excipients 16. Patients with tuberculosis or other severe infections such as (non-COVID-19) sepsis, abscesses, and opportunistic infections requiring treatment 17. Patients with moderate or severe heart failure (NYHA class III/IV) 18. Any other indication or medical history, that in the opinion of the local investigator means the patient is unsuitable for trial participation Duration of Effective Contraception (after last dose IMP) Arm 2: Gemtuzumab Ozogamicin FEMALES - 7 months (must use 2 effective forms of contraception) * MALES - 4 months Arm 3: Namilumab FEMALES and MALES 18 weeks after the last administration of namilumab Arm 4: - Infliximab FEMALES and MALES 26 weeks after the last administration of Infliximab * If using hormonal agents the same method must have been used for at least 1 month before the trial dosing and patients must use a barrier method during that time period Original 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 |
| Date of first enrolment | 16/05/2020 |
| Date of final enrolment | 30/11/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
Edgbaston
Birmingham
B15 2TH
United Kingdom
South Wharf Road
St Mary's Hospital
London
W2 1NY
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Farnworth
Bolton
BL4 0JR
United Kingdom
Cardiff
CF14 4XW
United Kingdom
London
WC1N 3BG
United Kingdom
Swansea
SA6 6NL
United Kingdom
Sheffield
S10 2JF
United Kingdom
Sponsor information
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Research organisation
Government organisation / National government
- Alternative name(s)
- UKRI
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/05/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| 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 plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol (preprint) | non-peer-reviewed protocol in preprint | 12/02/2021 | 23/03/2021 | No | No |
| Preprint results | non-peer-reviewed results in preprint | 09/06/2021 | 11/06/2021 | No | No |
| Results article | 16/12/2021 | 20/12/2021 | Yes | No | |
| Protocol article | 11/11/2021 | 30/08/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
30/08/2022: Publication reference added.
20/12/2021: Publication reference added.
27/08/2021: The following changes were made to the trial record:
1. The primary and secondary outcome measures, inclusion and exclusion criteria were updated.
2. Trial website and total final enrolment added.
3. The following trial participating centres were added: Royal Bolton Hospital, University of Hospital of Wales, Cardiff, University College London Hospital, Morriston Hospital, The Royal Hallamshire Hospital.
11/06/2021: Preprint reference added.
23/03/2021: Preprint reference added.
16/03/2021: Internal review.
01/07/2020: The following changes were made to the trial record:
1. The interventions were changed.
2. The drug name(s) was changed from "Gemtuzumab ozogamicin (Mylotarg)" to "Gemtuzumab ozogamicin (Mylotarg), Namilumab, Infliximab (Remsima)".
3. The inclusion criteria were changed.
4. The exclusion criteria were changed.
5. The plain English summary was updated to reflect these changes.
30/06/2020: The following changes were made to the trial record:
1. Trial participating centres added: Imperial College Healthcare NHS Trust and John Radcliffe Hospital.
2. The plain English summary was updated.
14/05/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).
