Article No. 432
7 May 2021
In the past week or so, the possible trial of a new technology for treating aHUS, that we reported on in website article No 415 , has been announced on the ClinicalTrials.gov website. ( Note: it had apparently been included on the EU version of clinical trials on the 19th March!)
Crovalimab, as this complement inhibitor is known, is administered sub cutaneously. There is a work up dosing protocol from day one and each week until week five . Then a maintenance protocol at four weekly intervals takes over.
From today, 7 May 2021, the recruitment of potentially 90 patients ( 30 12-17 years , 45 18 -64 , 15 65+) to the trial is expected to begin
Some patient recruits will have not been treated with a complement inhibitor before, some will be switched from eculizumab/ Ravulizumab treatment and some will have that C5 polymorphism that prevents eculizumab from working. This trial will not include children less that 12 years old.
There is, not surprisingly, a long list of inclusion and exclusion criteria.
But little information about how switch patients are counselled and advised about the transition. Hopefully it will be their informed decision.
There is one primary outcome measure , the percentage at 25 weeks with complete TMA response , cTMAr ( at what ever that means) , and twenty four secondary measures, mostly from clinical tests. Usual adverse events stuff is included but nothing which asks how the patients feel about their health at the end of it.
There are 71 recruiting sites in 17 countries, including the USA (16 hospitals) Belgium (1), Brazil (5), Canada (3), China (2), France (5), Germany (5), Hungary (1), Israel (3), Italy (4),Japan (4),Mexico (4), Peru (2), Poland (4), South Africa (2), Spain (4) and Turkey (6).
Most noticeably none in Australia* , India, New Zealand , South Korea* , Switzerland , The Netherlands, nor UK*.
The trial will last until 2024, with further three years follow up.
For those with a C5 polymorphism the trial provides an option for their unmet need at present.
For those who have been treated with eculizumab, but not Ravulizumab, it provides the chance to increase the interval between treatments, and hope that it is just as effective a treatment. There may also be some insurance excess cost saving for the duration of the trial.
Those already on four week eculizumab regimes do not get that benefit of a longer interval, but they may prefer an injection to an infusion , or not. It is not clear whether that injection is self administered, which might have an influence on some.
Those on Ravulizumab 8 week intervals will have to weigh up whether it is worth going backwards in terms of treatment interval.
Maybe aHUS patients will have more options to ravulizumab in 2025 or after as a result.
* Australia, South Korea and UK had been included as “planned countries” in the European Trials entry.