Key highlight number 2 says "Phase 2 clinical study in aGvHD...

Key highlight number 2 says

"Phase 2 clinical study in aGvHD expected to commence subsequent to customary and satisfactory completion of negotiations with study centres and receipt of relevant ethics/administrative approvals. "

Ross Macdonald wrote:

"We are delighted to have crossed this threshold and will continue to leverage the momentum in our negotiations with study centres with an expectation to commence a US trial in aGvHD by the end of the year".

So I'm currently reading "study centres" as meaning sites like major hospitals etc that might agree to take up CYP-GvHD-P2-01, the proposed protocol.

It seems that before patients can be recruited into the protocol they have to first recruit at least some study centres that will in turn be willing to run the protocol which involves the study centres agreeing to some administrative approvals and to some ethics aspects.

At present I'm wondering about the ethics aspect from this standpoint.

"After enrolment upon meeting eligibility criteria, participants will be randomised to receive either corticosteroids plus CYP-001 or corticosteroids plus placebo". It is not stated whether the randomising with be 30 to treatment 30 to control or 40 to 20 etc. This might matter. To be persuasive the trial has to be appropriately statistically powered - ie - there has to be enough in the control (placebo arm) to find statistically significant differences between the arms.

But the patients have already been identified as High Risk acute GvHD.

Consider from the announcement itself - "When GvHD fails to improve or worsens despite steroid treatment, patients are described as having steroid-resistant acute GvHD. The prognosis for these patients is poor, with mortality rates in excess of 90 percent". (Then there is a 2011 reference paper).

If that 90% figure is correct - doesn't that suggest almost a death sentence for those unlucky enough to get assigned to the control group?

That might not be an ethical problem (or even a tough decision for patients and their doctors to make) if there were really no other treatments than steroids or CYP-001 potentially available to the patients with HR aGVHD because their chances would be better on the trial than not and they'd be randomly (so fairly) assigned to either arm.

But what if at the time the patients are considering enrolling (or their doctors are considering whats in their best interests) there are other alternatives like off label treatments, or possible treatments that might be plausible alternative secondary treatments after steroid failure?

One possibility might be, perhaps MSB might have approval for pediatric aGvHD by 2023 or 2034 which might mean doctors might have an option of trying to get their adult patients onto an off label use for adult sr-GvHD.

If its approved it kids, because the FDA is satisfied its effective in kids, then will doctors still be willing to recommend adults take up the phase 2 CYP trial where they may be assigned to the placebo group rather than try to get off label use for the patient?

And its not just MSB, there are other potential secondary treatments that might come along that are not steroid based.

Recruiting study centres that are willing and able to recruit patients in the timeframes likely to be relevant say from the end of the year over the next year or two might prove to be quite tricky given the other things that may happen to affect the overall risk profiles of adult patients with aGvHD.

Good scientific method may prefer randomised controlled trials - but if we ourselves were patients with GvHD or doctors of patients with GvHD we'd probably have little trouble considering ourselves or our patients as having interests of their own that might not line up directly with doing good science for other peoples benefit.

I think recruiting is going to be a challenge, but we shall see.