Trial of CT38 for ME/CFS by Cortene Inc.: big claims being made...

I came across the following. I have no idea whether it is newly available or not:

 

My summary of the results:

A small improvement on self-reported outcomes with the lower doses, no improvement or small worsening with the larger doses.

This patter is seen in all outcomes.

Sample sizes are very small.

Under serious adverse events, one occurrence of tachycardia and hypotension is listed. The authors say this was due to a dosing error.

The list of non serious adverse events suggests side effects are very common, in particular headache. There is also one event of suicidal ideation. The list suggests this drug is very stimulating.

The original plan included measurement of daily steps. These outcomes were not reported.

 

Yes. However I suspect if the sample size was larger there might have been statistically significant and dose-dependent changes. Whether these reflect an effect on the illness would have been unclear. With side effects so prominent it could also be difficult to blind patients.

 

Updated website I think.

https://corteneinc.com/development/

 

None of those conclusions are justified given the tiny sample size and no control group.
The claims of CRHR2 upregulation do not seem to be associated with any (hitherto) published data.

The higher dosage may have resulted in slightly lower symptom scores in 2(!) participants, but one of those participants also suffered from tachycardia/hypotension, which is expected given that urocortin II (a CRHR2 agonist) is known to cause this. https://pubmed.ncbi.nlm.nih.gov/15476938/

 

https://clinicaltrials.gov/ct2/show/results/NCT03613129

I thought there was a placebovgroup, bad memory maybe. So 14 pateints, no placebo group, a very weird primary outcome TDSS and are those massive confidence intervals in parentheses next to the outcomes?

For all groups pretreatment baseline is 29.5, post treatment 25.3. That's about a 13% improvement, which seems similar to what you would expect with placebo group given this is an unblinded infusion.

Interestingly their is no clear evidence of dose-dependent response from lowest to highest (3.2, 7.5, 1.8, -2.9). Imo too little data and too few points to claim a peaking at the second dosage.

For secondary outcome SF-36, the group with the most improvements scored lowest at baseline, and for SF-36 both highest and second highest dosage showed negative or neutral outcomes.

The best result in the best dosage is about a 6 point improvement taking them to.... 30.7 on a SF-36 0-100 scale from 24.6. This is where the 26% improvement # comes from on cortene's update (even though its 25.1%). Putting it as a percent is kinda misleading to how large the improvement was. Going from 2 to 4 is an 100% improvement but it's also a 2 point one on a scale of 100.

edit 2: I wanted to reference these results a placebo infusion in me/cfs from RituxME. It may be expectations were higher for that drug, and I couldn't find the raw SF-36 numbers at 8 weeks, but it looks like cortene compares unfavorably to both the placebo and the failed intervention.

So going up 6 points is a relatively minor change in the illness, again with no "no treatment group" it looks even worse.

I do get it's only a phase 1 trial but given the context, it's hard to imagine justifying optimisim in this drug. There are quite a few side-effects as well, including fatigue and most patients had a headache. It'll be interesting to see if the Bateman Horne center continues to be involved.

edit: I just saw others had looked at this, I thought it was new info my mistake.

 

From: https://corteneinc.com/development/

1. is pure speculation as no direct measure of CRF2 expression or function was used.
2. is probably justified, but none of the other claims are justified as there was no comparison group.
3. Claims about efficacy are not justified from the data, due to to the fact that this is a pilot study (with a tiny sample size and no control group to boot!).

But more importantly, the drug, which is a peptide that has a short half life (as all peptides do), was only infused on 3 separate days. Which begs the question, what kind of treatment would be necessary to lead to the hypothesised desensitisation of CRF2 receptors? I'd suggest 4-6 weeks at least. Which leads me to believe that I we cannot assume anything about the efficacy from the data presented so far.

 

Yet more big claims being made. They link to the full text of their paper in the press release (my brain can't handle reading it).