Sunday, April 19, 2015

ATG and GCSF Combination Starts a Phase-II Trial


ATG is Anti-Thymocyte Globulin, a biological agent used to lower immune reactions.
GCSF is Granulocyte Colony-Stimulating Factor, a biological agent which causes bone marrow to generate more stem cells and more immune cells, and put them into the blood stream.  It is sometimes called G-CSF, and the exact product being used is Neulasta.

So the two of them together could make an effective combination therapy against type-1 diabetes. ATG would lower the autoimmune attack, and GCSF would help the body regrow beta cells.  At least, that is the hope. I wrote a more detailed blog entry on this combination four years ago, which you can read here:
http://cureresearch4type1diabetes.blogspot.com/2010/08/atg-gcsf-starts-phase-i-clinical-trial.html

ATG and GCSF Combination Starts a Phase-II Trial

This is a three armed study.  Each group will have at least 28 people.  The first will get ATG.  The second will get ATG and GCSF.  The third will get a placebo.  The ATG will be given twice, one day apart.  The GCSF will be given six times, two weeks apart. They started recruiting in December 2014, and hope to finish collecting their data in October 2016.  The primary outcome (the most important result they will measure) is C-peptide generation after a meal as measured a year after treatment.  There are no secondary outcomes listed, however I've been told they will track A1c, insulin usage, low BG, adverse effects, and infection rates as secondary outcomes.

They are recruiting in at least six different locations, all over the United States.  Although it's not listed on the clinical trial site, Stanford is recruiting for this trial, and they are planning on adding UCSF soon as well.  The list (with contact information) is in the Clinical Trial Record below. Patients must be between 12 and 46, and have been diagnosed within a 100 days,so this is a honeymoon trial.

Recruiting Site: http://www.diabetestrialnet.org/ATG-GCSF/index.htm
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02215200
Press Release: http://jdrf.org/2015/01/unlocking-a-combination-therapy-for-new-onset-t1d/
Wikipedia: http://en.wikipedia.org/wiki/Anti-thymocyte_globulin http://en.wikipedia.org/wiki/Granulocyte_colony-stimulating_factor

Funding for this trial comes from several US government agencies, JDRF, ADA, Helmsley, and two commercial companies: Sanofi and Amgen.

Discussion About Previous Results

For me, the most important question in a phase-II trial is: "What happened in the phase-I trial?"  If there was a phase-I trial.  For this treatment, there was and it included a placebo group.  The results were good, but not great, from the point of view of curing type-1 diabetes.  Over the years of the trial, the placebo group had lower C-peptide levels (meaning they lost the ability to make their own insulin). This is what would be expected during the years after diagnosis.  The treated group's C-peptide levels stayed about the same.

Obviously, an optimist will look at those results, and say "they stopped the loss, this is good, and the earlier we can use this, the better it will be".  A pessimist would say "they had type-1 when the trial started; they had it when it was over; there was no real improvement".

My blog on their previous results is here:
http://cureresearch4type1diabetes.blogspot.com/2014/07/ada-2014-type-1-diabetes-cure-research_14.html

And here is the most important graph from those results, you can see that treated people stayed the same (dark line at top) while untreated people got worse (lighter line below):

The full paper is here: http://www.jci.org/articles/view/78492.
Thanks to the The Journal of Clinical Investigation for making the whole paper available on line.

Joshua Levy 
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

3 comments:

Krisz said...

Hi,

what do you think about this? https://clinicaltrials.gov/ct2/show/NCT01762644?term=iit&rank=1
I know you have already written about perle bioscience 2 years ago, but now they move forward...
greetings from Hungary :-)

Mildly Feasible said...

My main question is related to the generation of Beta cells after the immune system no longer recognizes them as a threat.

Have there been any studies done showing the regenerative properties of Beta cells after immune system blockage? And would stem cells be needed after the immune system is successfully pacified? Thanks for the great post.

Joshua Levy said...

Krisz: I think the paperwork for that study was filed over 2 years ago, and so far nothing has happened. I heard a rumor that they would start in a month or two, but I think I've heard that before. In any case, I'll blog on them when they start recruiting people for the study. Until then, there is no new news, so I don't have an opinion. --Joshua