Replies to post #253442 on Innovation Pharmaceuticals Inc (IPIX)

[georgejjl]

The interim data revealed an unusually high placebo rate of clinical remission (24 percent, approximately four times higher than historical norms for similar UC studies) that led to a futility decision and discontinuation of the trial."

If the placebo clinical remission rate was 4 times normal, then that begs the question if some of the subjects that were thought to be on placebo were actual on the active trial treatment.

GOD bless,

George

[georgejjl]

In March 2018, Protagonist announced discontinuation of the study following a planned interim analysis conducted by an independent Data Monitoring Committee (DMC). The interim data revealed an unusually high placebo rate of clinical remission (24 percent, approximately four times higher than historical norms for similar UC studies) that led to a futility decision and discontinuation of the trial. A re-read of the endoscopies by the CRO's subcontractor and a subsequent fully blinded re-read of the endoscopies by an independent third party, Robarts Clinical Trials, confirmed that a subset of the initial endoscopy reads provided by the CRO were in error. If the re-read of endoscopy results had been utilized for the interim futility analysis, the trial would have continued. Results of the complete data set as read by Robarts are summarized below. In addition, improvements observed in independent, blinded histological scores favor PTG-100 over placebo and correlate with the clinical remission and endoscopic response outcomes from the re-analysis.

https://www.prnewswire.com/news-releases/final-results-from-the-protagonist-propel-study-support-further-clinical-development-of-ptg-100-for-the-treatment-of-ulcerative-colitis-300692199.html

GOD bless,

George

[PlentyParanoid]

In March 2018 Protagonist cancelled a trial of PTG-100 on ulcerative colitis based on CRO's bad endoscopic data (stupendous placebo rate seems to have been part of the problem).

My link was to later developments (August 2018) when it had become clear that Protagonist's CRO had messed up royally. New analysis of the discontinued trial: drug shows promise in ulcerative colitis contrary to earlier results.

The problem: new results were obtained from small subject groups with only the highest dose, 900 mg, showing promising separation from placebo. But still at p value of 0.33 only (memory refresh - prurisol 200 mg had ITT p value of 0.32).

Protagonist is now in a situation where it either
a. runs 200 subject dose finding study again to get indication if the trend for 900 mg holds
or
b. tries to convince FDA that current results will warrant phase 3. FDA may approve, but may also require larger trial(s) than it would have if the 200 subject trial had been completed successfully in the first place.
c. (later edit). abandon development of PTG-100 in UC. I admit that his alternative may results in savings when compared to completed 200 subject study, if that trial had still failed.

So, we have the cost of discontinue trial. Plus about 6 months of lost time (that has a cost). Plus cost of reanalysis. Plus potential cost of running dose finding study again (I think it is a strong possibility). Can you really say that this has resulted in obvious savings for stockholders? Maybe, if Protagonist decided to abandon PTG-100 in UC - otherwise I don't see it.

Modest proposal for entertaining pastime: Maybe we should start wondering what the possible re-analysis of prurisol p2b will bring. It could be that this was the hidden meaning SS wanted to bring to our attention.