Replies to post #9651 on Pluristem Therapeutics Inc (PSTI)

[HappyBee]

Hello Straightshot, I had many questions regarding clinical trials myself. This is a highly specialized field and I would hesitate to give you an opinion on your specific questions. I am posting two links that hopefully clarify certain issues. I found the information very helpful.

Regarding the first link (I recommend to read the whole document), page 9 discusses endpoints and page 14 clinical trials in more detail. On that page there is reference to a Data Safety Monitoring Committee. The second link (from the EMA) will explain that further. I hope this helps. Apologies for not being more specific, but I want to avoid at all cost writing something that could be seen as misleading. Best wishes, HB

http://www.esourceresearch.org/eSourceBook/ClinicalTrials/1LearningObjectives/tabid/192/Default.aspx

http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003635.pdf

[Spideyboy]

Hi Straightshot, and first of all you're right it is a bit unusual to have this relatively ambiguous Primary End point.

While this article is somewhat old (2012), given the apparent lack of progress in treating CLI I would expect much of these statistics to remain the same.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440268/

One year after diagnosis of CLI, 25% of patients have died, 30% are alive with amputations, 20% have ongoing symptoms, and 25% have symptoms resolve.

Now I'm sure that clinicians will have similar data with respect to different grades of severity on the Rutherford scale. PSTI is enrolling those of category 5 for the Phase III. (the Phase II included categories 4 & 5, but I'm sure PSTI has more data for a rationale to specify the category 5 for the Phase III)

We can see from the clinicaltrials.gov website (https://clinicaltrials.gov/ct2/show/NCT03006770?term=pluristem&rank=1) that the Timeframe for observing the patients is a follow up of 12 to 36 months (and seen from their latest presentation slide 17, and from website too). Thus this should provide ample time to show a clear difference in performance of the placebo vs treatment group.

Also this is why the trial can get preliminary approval early in Europe with the Adaptive Pathways pilot project granted for the CLI Phase III with results from 50% of the randomised sample. Is that once having half the sample we will also be somewhere around 1 year of treatment. Thus the interim data can be compared with such historical data as above, and an analysis of statistical difference can be performed.

They can start with the interim analysis that hopefully will show at worst a trend, or at best already statistically significant benefits.
It is also pertinent to note that in the presentation slide 18, it is stated that for the interim analysis they will also be generating that primary goal on the composite end-point which may facilitate early approval.