UK-CTAP meeting, 10 June 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, outlined the role and terms of reference for the group. No objections or observations were made.
2. Conflicts of interest
Chair asked the subgroup members to raise any conflicts of interest.
It was noted that conflicts should be raised throughout the meeting in relation to specific proposed compounds.
Frederick Hayden [redacted, General Data Protection Regulation]
Recusal from voting.
No other conflicts were recorded.
3. Drugs discussed and decision
Sub-group chair presented the advice of the antiviral subcommittee meeting for compound [redacted for commercial sensitivity].
3.1 [Redacted for commercial sensitivity]
[Comment redacted for commercial sensitivity]
The panel raised concerns over the need for continuous intravenous (IV) infusion for 5 days in a hospital setting and drug bioavailability both of which were considered a major limitation and will affect scalability.
It was also noted that continuous IV infusion also contains sodium chloride which could be a significant issue for some patients in the expected high quantity associated with continuous infusion
As a more general point, the panel noted that there is lack of data on drug resistance emergence for antivirals when used as monotherapy, and no specific data.
In 14 day good laboratory practice toxicity studies there was evidence of systemic inflammation and activation of the coagulation system in cynomologus macaques.
The preliminary clinical safety data for single and multidose study trial are limited as studies have not yet been completed. Panel expressed preference to wait for ongoing study results. Panel agreed that if this agent goes forward there would be a need for careful monitoring of prothrombin time, activated partial thromboplastin time, D-dimer, and fibrinogen levels, with samples stored for further coagulation factor monitoring if needed.
Drug safety was a concern in terms of complex drug interactions including with dexamethasone. Concerns raised over the potential for substantial higher drug exposures and thrombosis in the hospitalised patients.
The combination of this compound with remdesivir, [redacted for commercial sensitivity] could be considered. The combination of protease inhibition with nucleoside analogues has been an effective antiviral strategy in other diseases. The risk of predictable drug-drug interactions with remdesivir is low.
Agreement that this should not be recommended into any clinical trial platforms at this moment in time. But the panel will await to see the full [redacted for commercial sensitivity] study trial data and safety data.
The panel advised the sub-group to continue to monitor the clinical trials and get further information from the sponsor on in vivo antiviral effect against SARS-CoV-2 in tolerable doses.
Additionally, the panel would like to see combination testing with remdesivir.
Chair thanked the group and closed the meeting.
- Patrick Chinnery (Chair)
- Michael Jacobs
- Frederick Hayden
- Charlotte Summers
- Ian Hall
- Duncan Richards
- Moira Whyte
- 3 trial investigators
- 1 Department of Health and Social Care representative
- 8 secretariat members
- Munir Pirmohamed