UK-CTAP meeting, 11 January 2021.
Held via video teleconference.
Some information has been redacted for the reasons listed in ‘details’ for UK COVID-19 Therapeutics Advisory Panel: records of decisions.
1. Welcome and introductions
Chair welcomed the group, acknowledging the new year.
2. Governance: conflicts of interest
The Chair asked members to declare if any new conflicts of interest had arisen
Declarations
Ian Hall [declaration redacted, GDPR]. Will recuse for any decisions regarding the relevant compounds.
Charlotte Summers [declaration redacted, GDPR]. No action required for this meeting.
Frederick Hayden [declaration redacted, GDPR]. Will recuse for any decisions regarding the relevant compounds.
No other conflicts were recorded.
3. Drug discussion
3.1 Baricitinib
The chair introduced the item referring to the committee discussion by email.
The panel discussed the use of baricitnib with remdesivir, dexamethasone and tocilizumab.
The panel discussed dosing information arising from ACTT2 and ACTT4 studies.
The group noted that many patients in RECOVERY+ would be taking remdesivir or dexamethasone as standard of care.
The group noted potential toxicity concerns of using baricitinib with tocilizumab.
Recommendation or action
Recommended for phase 3 RECOVERY trial at 4mg total daily dose, contingent on the pending read out of tocilizumab.
Baricitinib should not be used in combination with tocilizumab.
3.2 Dimethyl fumarate
The chair introduced the item referring to the phase 2 endpoint workshop of 8 January 2021, where dimethyl fumarate had been used a ‘strawman’ test case.
The panel noted that dimethyl fumarate has a well understood clinical profile in multiple sclerosis and psoriasis, and that there was a plausible case for efficacy in COVID-19.
The panel agreed a phase 2 trial to establish an efficacy signal in COVID-19 patients was required before consideration of phase 3 trials use.
Recommendation or action
Recommended for phase 2 RECOVERY trial.
The dose regimen will be informed by pharmacokinetic (PK) modelling.
3.3 Favipiravir
A proposal for a five-day course of treatment was presented.
The panel considered tablet burden and views on five, seven and 10-day course of treatment.
The panel noted issues arising from packaging which would impact the speed with which trials could be started.
Recommendation or action
Recommended that PRINCIPLE should use a five-day regimen.
4. Immune subgroup advice
The subgroup chair presented baricitinib and dimethyl fumarate as noted above.
The panel considered the advice of the subgroup arising from their meetings of 30 November 2020 and 16 December 2020.
Recommendation or action
The panel asked that ivermectin be revisited subsequent to meta-analysis of World Health Organization data.
The panel accepted the advice of the subgroup arising from their meetings of 30 November 2020 and 16 December 2020.
5. Cell therapy subgroup advice
The chair confirmed the 25 November 2020 advice had not changed from the draft reviewed at the last UK-CTAP.
Recommendation or action
The panel endorsed the advice of the subgroup on recommendations and prioritisation.
6. Antiviral subgroup advice
The subgroup chair led a discussion on the dosing regimen for favipiravir in the PRINCIPLE trial as noted above.
No observations were raised with the 28 October 2020 or 10 December 2020 advice.
The panel noted that there was an increasing need to explore antiviral combination to address both efficacy in treatment and potential antiviral resistance.
Recommendation or action
The panel endorsed the advice of the subgroup on recommendations and prioritisation.
UK-CTAP secretariat to develop a proposal to explore antiviral combination therapy.
7. General discussion on approach
An update to the group on progress to date was presented.
The panel noted that the presentation did not reflect all of the progress made because the classification system did not distinguish between drugs known to be in trial from those not yet considered in detail because they were already in trial.
Panel members agreed that the work of the due diligence team had been extremely beneficial and of a very high quality leading to informed decision making by UK-CTAP.
The panel made the following recommendations to enhance the operation and outcomes of UK-CTAP:
- Re-classify prioritisation to note submissions which are pending the outcome of existing trials before processing, to differentiate them from submissions which have not been processed at all.
- Batch submissions which have a low probability of efficacy or do not have enough information for consideration. This would allow subgroups and panels to formally comment on them and reduce the perception of a back log.
8. HEAL-COVID platform
The HEAL-COVID platform was outlined and the panel noted US and Chinese published data highlighting 20% of patients are readmitted or die within 90 days of discharge after COVID-19. This was supported by UK Office for National Statistics (ONS) data from Scotland suggesting one in 10 people still have significant symptoms 12 weeks after being diagnosed with COVID-19.
The panel noted the trial had pilot funding from Department of Health and Social Care and the NIHR Cambridge Biomedical Research Centre to study post-hospital COVID-19 pending the outcome of an NIHR Health Technology Assessment panel which has been convened to evaluate the full proposal. HEAL-COVID has asked UK-CTAP to recommend therapies for inclusion in the study.
The therapies considered by the HEAL-COVID team are:
- aspirin
- statins
- metformin
- steroids
- anti-fibrotics.
Recommendation or action
UK-CTAP to recommend first compounds by 25 January 2021.
Attendees
Scientific experts
- Patrick Chinnery, Chair (Medical Research Council)
- Munir Pirmohamed
- Moira Whyte
- Duncan Richards
- Ian Hall
- Charlotte Summers
- Frederick Hayden
- Michael Jacobs
Observers
- six observers
Secretariat
- nine members