Agenda or minutes

10 February 2021 UK-CTAP: record of decisions

From:
UK-CTAP
Published:

UK-CTAP meeting, 10 February 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.

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 declared:

  • [declaration redacted, GDPR], no action required for this meeting
  • she is co-investigator on HEAL  trial, will recuse herself from decision on  HEAL.

Duncan Richards declared he is co-investigator on HEAL  trial. Will recuse himself from decision on  HEAL.

Frederick Hayden [declaration redacted, GDPR]. Will recuse for any decisions  regarding the relevant compounds.

No other conflicts were recorded.

3. Confirmation of agreement by email

The chair confirmed the recommendations made out of committee.

This was for colchicine into PRINCIPLE, adalimumab into PRINCIPLE, an anti-complement agent into RECOVERY+ and niclosamide (lower dose: intranasal and inhaled formulation) into AGILE.

Secretary’s note: the exact anti-complement inhibitor to be decided by triallists as the panel agreed this was a class effect.

4. HEAL-COVID

The HEAL-COVID co-investigators presented an outline of the platform to help the panel in their consideration.

The panel noted that the trial was currently looking to identify one or two interventions likely to have an impact on morbidity and mortality. The intention of the trial was to find broadly applicable compounds that could be utilized across a range of populations and administered with GP support.

5. Drug discussion

5.1 Statins

(Charlotte Summers and Duncan Richards observed as co-investigators, in line with panel norms.)

Statins had to be brought direct to UK-CTAP as their action could be viewed as cutting across multiple mechanisms of action.

There was evidence for a class effect and the safety profile was well understood.

The panel clarified that statins could be considered for any of the UK-CTAP aligned trials, but the co-investigators had submitted for consideration for the HEAL-COVID platform.

The panel noted that statins had a wide range of effects, but the onset of that effect made them unlikely to be effective in an acute setting.

The panel agreed the was a plausible rationale for inclusion into HEAL-COVID, with an expectation to lower hospital readmission.

The group noted that 30% of the target population may already be using statins and therefore ineligible for trial.

The panel considered water- and fat-soluble statins agreeing that atorvastatin as the optimum choice as the likelihood of drug-drug interaction was lower.

Recommendation or action

The panel recommended atorvastatin 40mg to HEAL-COVID trial.

5.2 Almitrine bismesylate

The chair introduced the item noting that almitrine bismesylate was not currently licensed in the UK but had seen short term use in France. It was highlighted as a potential for phase 2 trial.

The panel clarified that it was not within their remit to comment on any questions of UPH badging for [trial name redacted].

The panel noted there was some clinical evidence of improved oxygenation in acute respiratory distress syndrome (ARDS) and that the rationale in the proposal for COVID-19 was the shunting effect of almitrine bismesylate.

Recommendation or action

Recommendation that almitrine bismesylate is not currently prioritised for inclusion in UK publicly funded trials.

5.3 Ivermectin

The meta-analysis provided in the papers was highlighted to the panel. The panel considered whether this analysis would cause them to review their recommendation not to prioritise ivermectin.

The group noted the Merck statement on ivermectin.

The panel agreed that the meta-analysis supported the panels original recommendation not to prioritise ivermectin.

The panel expressed discomfort at any potential inclusion of ivermectin into a UK publicly funded trial, reconfirming its view there was no plausible rationale for inclusion and noting there was an opportunity cost in terms of patient numbers that could be recruited into a trial with a more plausible expectation of efficacy.

The panel noted that if a drug were taken into trial specifically to provide a definitive outcome of ‘no efficacy’ it had ethical implications.

Recommendation or action

Confirmation of the recommendation that ivermectin is not currently prioritised for inclusion in UK publicly funded trials.

6. Prophylaxis subgroup advice

The subgroup chair noted that this was the first prophylaxis subgroup to sit (in the new CTAP structure) and thanked the Due Diligence Team for the high quality of briefing papers.

The group noted that it was likely that successful prophylactics would show some signal in a treatment setting.

The panel considered the advice of 13 January 2021.

Recommendation or action

The panel asked the subgroup to explore the concept of prophylaxis driving resistance and mutation.

The panel endorsed the advice of the subgroup on recommendations and prioritisation.

7. Immune subgroup advice

The subgroup chair presented three drugs of interest.

7.1 [Treatment redacted]

UK-CTAP discussed via email. The advice was to review after the RECOVERY+ readout on tocilizumab.

7.2 Namilumab and infliximab

The advice of the subgroup was that namilumab and, or, infliximab could go into REMAP-CAP (ranking namilumab > infliximab) in a specific group of patients who are not responding to tocilizumab.

For RECOVERY+, one or both could be included in the trial pending readout from other drugs being trialled in RECOVERY+. For example, if baricitinib reduces mortality, it would be very difficult to use either of these drugs on top of baricitinib which would become standard of care.

The panel considered the advice of 16 December 2020 (amended), 13 January 2021 and 2 February 2021.

Recommendation or action

The panel agreed [treatment redacted] should be reviewed after the RECOVERY+ readout on tocilizumab.

The panel recommended namilumab into trial with REMAP-CAP.

The panel agreed that considering recent immunomodulator recommendations that namilumab and infliximab should be added to a shortlist with the others, to prioritise at short notice when new arms become available, based on emerging trial data and the logistics.

The panel endorsed the advice of the subgroup on recommendations and prioritisation.

8. Thrombostasis subgroup advice

(Charlotte Summers and Duncan Richards observed the HEAL-COVID recommendation as co-investigators, in line with panel norms.)

The subgroup chair noted that new data submitted regarding [treatment redacted] did not satisfy the subgroup and additional safety data was required if it were to be reconsidered.

The alternate subgroup chair presented direct oral anticoagulants (DOACs) noting there was a plausible case for short term thrombo-prophylaxis. The subgroup advised apixaban 2.5mg twice daily for a two-week course should be considered for HEAL-COVID.

The panel considered the advice of the meeting of 20 January 2021.

Recommendation or action

The panel recommended apixaban 2.5mg twice daily for two weeks.

The panel endorsed the advice of the subgroup on recommendations and prioritisation.

9. Antiviral subgroup advice

The subgroup chair led a discussion on the considerations for combination antivirals, noting there was no clear evidence for one combination over another.

The panel agreed there was a need for in vivo data, early clinical trials and pre-clinical trials of new compounds.

The panel heard advice from the subgroup on proposals for the use of convalescent plasma in prophylaxis and treatment settings.

The panel noted there were significant logistical challenges in deploying convalescent plasma and the potential to drive resistance.

The panel agreed that detailed feedback on RECOVERY+’s convalescent plasma trial was needed to make a definitive recommendation on the likely efficacy of plasma and blood related products.

The panel explored whether a nosocomial trial would benefit the trial of convalescent plasma and other interventions targeting early onset COVID-19.

The panel heard advice regarding [treatment redacted]. The subgroup suggested waiting for the outcome of the [redacted] study or other in vivo data, prior to any recommendation.

The panel considered the advice of the meeting of 26 January 2021.

Recommendation or action

UK-CTAP Secretariat Due Diligence Team to prepare a comparison of convalescent plasma, immunoglobulin and mono-clonal antibodies.

The panel recommended the commissioning of a nosocomial trial.

The panel endorsed the advice of the subgroup on recommendations and prioritisation.

10. Any other business

10.1 Phase 2 compounds

The panel noted that UK-CTAP had a remit to recommend compounds for phase 2 trials and subgroups should ensure their considerations addressed this imperative.

The groups suggested increased proactive communications, particularly highlighting our phase 1 to 3 pipeline would be beneficial in increasing submissions to UK-CTAP. The group noted that UK-CTAP related trials represented exceptional value for money for pharmaceuticals and highlighted the benefits of drug development and trialling in the UK.

10.2 Subgroup membership

The chair thanked the panel for its commitment, noting the efforts that panel members and subgroups had made in the period. Acknowledging the voluntary nature of panel and subgroup membership the chair asked panel members to consider whether their subgroups needed refreshing.

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

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