@Bazsa
Hi,
Noted your points re the crossover populations. I too feel Dr L. is likely further along in both 1B/2A trials NCT04548583 (link) and NCT04543994 (link), despite both still trials showing their status as 'recruiting', and despite the notional 2023 end dates. I applaud that Cleveland Clinic have notified NIH that they don't intend sharing individual patient data under IPD sharing. Good, lets keep everything commercial in confidence for now.
Good point regarding the dosage change. I'd very much like to know with a degree of certainty what the drivers were for Dr L. - as an MSB investor I do hope that it was more than just availability of treatments in Ohio, although with COVID playing havoc with cold chain logistics I guess that's possible.
However, the NIH registry info shows the UC trial start date was Nov 10, 2020, and it was a 75 to 300m dosage change to the second intervention arm was made some time between Dec 4, 2020 and Dec 14, 2020. For Crohn's colitis the start date was Nov 4, 2020, and the 75 to 300m dosage change to the second intervention arm was made some time between Dec 2, 2020 and Dec 17, 2020. Interestingly, the UC trial had already reported the change of its 100 to 150m dosage in the first intervention arm between Dec. 2, 2020 and Dec 4, 2020. Similarly with the Crohn's colitis trial.
So, as I see it, with a start date of Nov. 10, 2020 it's possible that neither trial had finished its initial recruit screening, consent & randomising procedures to be able to apply any treatments to the first 12 patients by the time the dosage change was introduced. You'll rightly point out to me that these were both single-site studies (at Cleveland Clinic) & would have been well-controlled (in an admin sense), but I still think the processes could have taken a little time in those first few weeks in November/ December & Cleveland Clinic may have held off treatments for that short period while they sorted it out with MSB. I mean, COVID-19 was hitting its straps in Ohio right around then & Cleveland Clinic was being hit hard: Here's an example: https://www.cnbc.com/2020/11/24/close-to-1000-cleveland-clinic-caregivers-infected-with-covid-19.html.
I'll drop you a separate note regarding the controls crossover population & what I see as the possible additional scientific value in control crossovers into Dr L's trials, as the trial protocols and Dr L's poster abstracts suggest to me will occur. Also, the implications for powering on any in-house trial.
But briefly, compassionate reasons for crossover should be taken as the primary driver IMO & I'm sure you feel the same. Every time CEO Itescu presents to the market or potential investors, he reminds everyone that the plight of kids in SR-aGVHD is still his (& therefore, our) primary driver. Even if MSB hadn't offered the treatments to non-responder controls, I think any efhics committee members would ask the PI and sponsor here to consider it in trial design, given the severity of this unmet need. Here, I think the intent has been made clear (by Cleveland Clinic & indirectly MSB), & I expect MSB to incorporate similar crossove (for controls) into future trials, if scientifically possible without making the trial unworkable. Dr L has already made clear that in the treatment arms, non-responders will be taken back to full non-treatment options if they dont respond in relatively short order, & IMO that will of course include full surgical procedures, as necessary.
(20min delay)