Article No. 331
8 March 2020
During his talk about potential complement inhibitors, Dr Richard Smith mentioned a ClinicalTrials.gov clinical trial regarding eculizumab for treating COVID-19 or ‘corona virus disease 2019’ , the version of coronavirus sweeping the world. The audience attending the Toronto Complement Conference yesterday (7 March 2020) seemed amused.
But there actually is such a clinical trial, it was posted on 28 Feb 2020 and identified by trial number NCT04288713. It can be seen at this link HERE.
And a short news video of the investigator Dr Pitts explaining his translational research concept can be seen HERE .
At the end of the video the message was at 5 March “he doesn’t have any participants, no sponsors or backing from the drug-maker”.
This is the Brief Summary posted describing why this trial was proposed:
Covid-19 has spread rapidly throughout the world causing widespread panic, death, and injury. While this virus is the provocateur, it is often the patient’s own disproportionate immune response which deals the most devastating (and often fatal) damage. A specific part of the immune system, known as the complement, has been shown to cause such damage in other types of coronaviruses. In the SOLID-C19 study, Soliris (Eculizumab) will be used to modulate the activity of the distal complement preventing the formation of the membrane attack complex. By modulating this portion of the immune response, mortality can be halted while the patient has time to recover from the virus with supportive medical care.
So whilst this corona virus disease is seriously harmful, it is suggested that the complications caused by excessive and damaging complement ( possibly an “infection TMA”?*), including kidney failure, could be avoided and therefore COVID-19 patients could be given more time until the virus runs its course.
This is an expanded use trial for adults over 18 years, who are not intubated, and who test positive for COVID-19.
The usual precautions and dose levels for for loading and maintenance of eculizumab will apply. But the treatment will be terminated one month after the patient recovers from the virus infection.
The trial is being undertaken by Hudson Medical in New York.
Once recovered the patient’s blood will be collected and sent for possible recovery of an antibody with the hopes that it may aid in the creation of a vaccine against COVID-19.
The concept for this trial is based on the Gralinski Group study of Complement and the SARS version of coronavirus. That publication can be read HERE.
Gralinski et al’s conclusion was “data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.”
That is all that is known at present on this topic. As far as aHUS Global Action knows, Alexion has made no comment about COVID-19. aHUS Global action is not medically qualified to advise, but recommend patients to check with their own physicians or medical teams.
The reaction from attendees at the Toronto Complement Conference is understandable given the idea that a therapy as expensive eculizumab could be an answer for the treatment of possibly millions of people around the world, as COVID-19 may become more common. Many hearing the Dr Smith’s presentation in Toronto remain keenly aware that cost issues drive eculizumab access and result in many aHUS patients are denied access in countries around the world, which may account for conference’s swell of reaction.
There is a saying in the rare disease community that ‘investing in rare disease therapies can sometimes benefit the common‘. It makes you think.
This is a trial to watch.
*Infection: Infection TMA includes HUS, the typical form, which results from an e.Coli infection. This is more common than aHUS and has been regarded as a different disease, although there is some overlap if a patient is found to have one or more Complement mutations. But there are more infections that can trigger HUS including streptococcal pneumonia, a rare trigger of aHUS and sepsis. HUS by definition excludes aHUS and there is no strong case for it to be included in “new aHUS”. TMAs resulting from other infections might be considered for inclusion, if they are a trigger for Complement variant TMA
The above is an extract from a website blog article about reclassification of aHUS https://www.ahusallianceaction.org/ahus-is-its-end-really-nigh-3/