I like that they are continuing to do the open-label study at the same time, for more immediate, even if less reliable, results. A steady drip of unblinded results until finally revealing the blinded results.
Trial Report Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al
V.R.T.
Senior Member (Voting Rights)
Yeah I really appreciate this approach too.
I doubt what the field of ME/CFS needs is more useless anecdata. What we need are usual standards, not a continous lowering of standards.
How would one ethically justify an unblinded study of 60 patients, especially after the Rituximab studies?
With the approach they have taken patients will either have access to an effective drug quicker or less people will be given a potentially harmful drug that does nothing. Win, win to me.
I think I’ve changed my mind about some of this. At first I thought a shorter study is better to get it done with. But now with certain people taking longer to respond to Dara (~6 months like the Twitter guy with SJ + ME/CFS) I think longer is better to tease out delayed/late responders.
But they do need to blind it.
But they do need to blind it.
Jonathan Edwards
Senior Member (Voting Rights)
Indeed. No brainer.
V.R.T.
Senior Member (Voting Rights)
Yeah I don't know about that account. Are there any other diseases where someone begins responding sixth months after recieving a monoclonal antibody @Jonathan Edwards
Jonathan Edwards
Senior Member (Voting Rights)
Not that I know of. Response can take 6 months to evolve and some patients are not at their best until after two cycles. But daratumumab may have different kinetics from rituximab.
Theoretically it would all depend on the mechanism of symptoms. Some changes might take 6 months to reverse and eah disease is different in the effector mechanism.
Not a mab, but IIRC the response for cyclo was around 6 months in the Fluge study.
V.R.T.
Senior Member (Voting Rights)
Until it began?
Not sure—can’t read paper now.
Most of the responses in cyclo and Dara are long ramps not cliffs, so my point is that waiting longer makes sense in that you can see the full effect.
If you give drug X to 2 ME/CFS patients one with a Bell score of 10 and one with a Bell score of 90, do they both respond at the same time or does the more severe notice the effect sooner? IDK, but maybe the less severe needs a longer time to notice a change?
Most of the responses in cyclo and Dara are long ramps not cliffs, so my point is that waiting longer makes sense in that you can see the full effect.
If you give drug X to 2 ME/CFS patients one with a Bell score of 10 and one with a Bell score of 90, do they both respond at the same time or does the more severe notice the effect sooner? IDK, but maybe the less severe needs a longer time to notice a change?
Utsikt
Senior Member (Voting Rights)
Participation takes 15 months for the participants. Enrolment might be finished in the summer. So the earliest the data gathering phase might be done (in theory) is in late 2027.
Then there’s the analysis (no idea how long it would take), and finally writing the paper.
I just hope they go for a preprint to get it out before the long peer review processes.
Then there’s the analysis (no idea how long it would take), and finally writing the paper.
I just hope they go for a preprint to get it out before the long peer review processes.
V.R.T.
Senior Member (Voting Rights)
Thats a good point, in the pilot they took months to reach a normal step count.
ryanc97
Senior Member (Voting Rights)
Meh, just my take on it. Or at least run a blinded and unblinded. But resources I guess.
Again my take here is the effect is too strong to be blinding and the question is what causes the response rather than is it placebo.
There is enough evidence for me that its not placebo:
1. The NK corr
2. The synchronized 8 week improvement
Again my take here is the effect is too strong to be blinding and the question is what causes the response rather than is it placebo.
There is enough evidence for me that its not placebo:
1. The NK corr
2. The synchronized 8 week improvement
ryanc97
Senior Member (Voting Rights)
Brainer!
jnmaciuch
Senior Member (Voting Rights)
Do we know what injection schedule the responders were on? The majority of participants had their last dose at 6 weeks. We definitely can't discount the possibility that most participants waited until they got their first "full course" before starting to test their limits. Especially if, in those earlier weeks, severe patients were conserving their energy just to make sure they made it to all the appointments. If the drug wasn't giving me energy like a stimulant, that's probably how I would behave.
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ryanc97
Senior Member (Voting Rights)
Well, the sf36 scores all went up suddenly at the week 8 mark, so testing limits would reflect in step counts rather than the sf36.
jnmaciuch
Senior Member (Voting Rights)
Yes, and around half of the questions are specifically about activity limitations, so they might be likely to reflect the same thing.
Utsikt
Senior Member (Voting Rights)
As mentioned before, there are LP anecdotes of people doing far more for longer than a year before collapsing. There are also anecdotes of spontaneous recoveries (like in the NIH study). So the changes seen in the pilot can in theory be explained by something other than that Dara works for some. Hence the need for a properly controlled trial to be sufficiently certain about the interpretation of results.
If bias can creep into a trial it usually does. We see this time and time again with treatments looking promising in smaller unblinded and uncontrolled studies, and then completely failing in larger studies with better methodology.
When you combine that with the cost of the drug (>1M£ total for ~40 people) and the complete lack of public funding or pharma sponsorship, the cost to benefit-calculation just doesn’t add up for another unblinded trial, other than what they are already doing with e.g. adding 5 severe patients to the pilot.
I have no issue understanding that people want results yesterday, but this trial really is moving as fast as possible.
If bias can creep into a trial it usually does. We see this time and time again with treatments looking promising in smaller unblinded and uncontrolled studies, and then completely failing in larger studies with better methodology.
When you combine that with the cost of the drug (>1M£ total for ~40 people) and the complete lack of public funding or pharma sponsorship, the cost to benefit-calculation just doesn’t add up for another unblinded trial, other than what they are already doing with e.g. adding 5 severe patients to the pilot.
I have no issue understanding that people want results yesterday, but this trial really is moving as fast as possible.