Dropping Four Research Programs

Every year in September or October I write a blog posting which summarizes all research being done in humans, aimed at curing type-1 diabetes.  That blog is going to be published in 2-4 weeks.   While putting that blog together I have found several research projects which I should not cover any more, and I'm listed those here, with a brief note on why they are no longer of interest.

I understand that this posting is a downer, and I'm sorry for that, but it is important to know what studies are no longer looking promising, and why.  Research naturally gets a lot of press when there is good news, but it's important to keep track of the bad news, and the "no news is bad news" situations as well.

Dendritic Cell Therapy  (DV-100) by DiaVacs
This trial was supposed to start in 2013, but never did.  The company is working on a follow on product, DV-200, and when that starts clinical trials I will follow it.  But since there has been a five year break between DV-100 and DV-200, I'm going to wait until a trial actually starts before restarting coverage.

BCG by Faustman at Harvard
This research is being removed for two reasons:

• Her phase-II trial is not using C-peptide data as either a primary or secondary outcome.  C-peptide is the standard measure for progress to a cure, so not having it as a primary or even secondary outcome means this research is no longer "aimed a curing type-1 diabetes".  (I will continue to follow it, and especially any C-peptide data that comes out, but unless C-peptides are a primary or secondary outcome, it is not cure focused for me.)
• The phase-I trial extended results show that Dr. Faustman's original theory (the TNF theory) of how BCG might cure type-1 diabetes is wrong.  The paper said specifically that the theory did not explain the results seen, and presented a new theory.  However the new theory is based on how the body digests carbs (not regenerating beta cells), and therefore is not a cure focused theory.  (Indeed, several type-2 diabetes treatments are based on similar theories).  So even if this theory is correct, the result would be treatment, not cure.

Obviously, this research group is continuing to talk about curing type-1 diabetes, but one the rules of my blog is "Actions speak louder than words" and if the clinical trial is not focused on C-peptide data, I don't think they are focused on a cure, no matter what is said.

Rilonacept by White at University of Texas

This group published their phase-I results in June 2018, but they were unsuccessful: "Rilonacept treatment for 6 months is well-tolerated in individuals with T1D of recent onset, but is unlikely to be efficacious as a single agent in preserving beta cell function."  So I don't expect any follow up work.

The Sydney Project (Encapsulated Stem Cells)
I can not find any recent references to this project.  The closest I can find is an encapsulated stem cell project being funded by the Australian Foundation for Diabetes Research.  It is doing animal research right now, so not clinical trials.


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, JDCA, or Bigfoot Biomedical news, views, policies or opinions. In my day job, I work in software for Bigfoot Biomedical. 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.

Possible Cures for Type-1 in the News (August)

More News on Rituximab

Background on the drug: Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's beta cells in the pancreas. By targeting the B cells, it is hoped this treatment will stop or lower the attack of the T cells. Rituximab showed some effectiveness in preserving the beta cell function of honeymoon type-1 diabetes in a phase-II trial, and there is a second trial underway. Rituximab is a monoclonal antibody, a product of Genetech (now a division of Roche), and already approved by the US FDA for rheumatoid arthritis and several cancers (and used off label for several other diseases).

Background on antibodies: Type-1 diabetes is triggered when the body's own immune system attacks it's own beta cells in the pancreas, which create insulin. Autoantibodies are part of the process of this self-attack. In type-1 diabetes four different types of autoantibodies have been measured: GAD, Insulin, IA2, and ZnT8. There might be a few more autoantibodies that we don't yet know about. People with type-1 diabetes usually have one or more autoantibodies in their system, and this starts before they are diagnosed. I think that GAD is the most common, and IAA is second, but I'm not up on the details.

For this study, 49 patients where given four doses of Rituximab, while 29 got the placebo.  For all patients, measurements were made for each different type of autoantibody.  What they found was that  Rituximab was very good at lowering IAA autoantibodies, but much less effective on the other three known types of autoantibodies.  This was the biggest finding:

A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients.

So that means that Rituximab was highly selective as to what antibodies it shut down. This is a very interesting finding, at least for me.  In terms of impact on patients, we need to see the C-peptide numbers, which were not in the abstract.

Next Steps?

In light of these results, one obvious clinical trial to run would be to treat honeymoon type-1 diabetics, who only have autoantibodies to IAA, with Rituximab, and see what happens.  The results above imply that over a third of these patients would end up having no autoantibodies remaining, and it would be very interesting to see what happens to these patients.  What effect will it have on their insulin production?  Will they still have type-1 diabetes?  Will their pancreases regrow?  If so, how quickly?  These are critical questions.

Another interesting clinical trial to run would involve patients that did not have type-1 diabetes, but were being tracked by TrialNet's Natural History Study, and are known to only have IAA autoantibodies.  Basically, does treating these specific people with Rituximab delay or reduce the onset of type-1 diabetes?

And finally, there is a potential study for established type-1 diabetics who only have IAA antibodies.  Would giving them this drug have good effects?

I have no idea if any studies like these are feasible, or are being planned, but I hope so!

Abstract: http://diabetes.diabetesjournals.org/content/early/2011/08/05/db11-0674.abstract
News article: http://www.doctorslounge.com/index.php/news/pb/22439
Wikipedia: http://en.wikipedia.org/wiki/Rituximab
More on Autoantibodies: http://www.msdlatinamerica.com/diabetes/sid683880.html


News about News on DiaPep277

DiaPep277 is the longest running phase-III study aimed at curing type-1 diabetes.  It is a honeymoon only treatment. Results from the phase-II study were (in my opinion) "mixed".  (I know that doesn't sound very definitive and I really should go back and review their phase-II results in more depth, but I haven't had time.)  My most detailed discussion of their phase-II results is here, but it's not much:
http://cureresearch4type1diabetes.blogspot.com/2009/11/possible-cures-for-type-1-in-news-nov.html
and all of my blogging on DiaPep277 (hsp60) is here:
http://cureresearch4type1diabetes.blogspot.com/search/label/DiaPep%20277

The following quote is from a news article on them, and is the most recent news I have heard about when they might have some phase-III results.  The key news is that the study should be done late this year, which is not very far away.  With a little luck, we'll see results in 2012.

In the first Phase III studies being conducted at 40 medical centers in Europe, South Africa and Israel, diabetes patients aged 16 to 45 have been receiving DiaPep277 injections once every three months. The study began in 2005 and is ending late this year.

They have a second phase-III study already underway, and expected to finish in 2014.  (Remember, you need two in order to get FDA or EU approval.)

News coverage: http://www.shalomlife.com/health/15810/promising-treatment-for-diabetes/

Rilonacept is Recruiting for a Phase-I Trial

I know there is a lot of frustration about  studies that are targeted at "honeymoon" diabetics.  And it is certainly true that most current trials are aimed at honeymooners.  However, "most" does not mean "all".  Dr. White is running a study on Rilonacept that is open to people within 5 years of diagnosis.  Also, this study has no placebo group, so if you are in the study, you know you are getting the treatment.

I have previously blogged on this clinical trial, which you can read here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Rilonacept

This drug is already approved in the US under the trade name "Arcalyst", but not for type-1 diabetes.  In addition to this approval, it is currently being used in about 12 other clinical trials for a variety of inflammation related diseases.  Dr. White has told me (via email) that there have been "no untoward effects thus far".  The trial is being run in Dallas, Texas.  Contact information is in my previous blogging (link above).

Trial web site: http://www.childrens.com/specialties/endocrinology/rilonacept-study/
Clinical Trial Site: http://www.clinicaltrials.gov/ct2/show/NCT00962026

Some Background Reading

Below is a link to a short interview with Dr. Arthur Caplan, a bioethicist at University of Pennsylvania, which makes for some interesting reading.  It is about the ethics of overseas medical research.  Something that we are seeing a lot of in type-1 diabetes research.  Dr. Caplan is an interesting guy and a good speaker.  UPenn is my alma mater:
http://www.pbs.org/newshour/rundown/2011/08/sending-us-drug-research-overseas.html

The following Wikipedia article covers accuracy of home glucose monitors.  Many people are shocked to learn that they are only accurate to within 20%.  So you might get 310, 340, or even 360 at the same time: http://en.wikipedia.org/wiki/Clarke_Error_Grid
Thanks to swellman at CWD for pointing this out to me and many others.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement. 
Blog: http://cureresearch4type1diabetes.blogspot.com
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news

Possible Cures for Type-1 in the News (Feb)

Rilonacept Starts a phase-I Clinical Trial

About six months ago, I blogged about three clinical trials which had not yet started, but were expected to start "soon".  Now the Rilonacept study is actually starting. 

This drug has not previously been tested on type-1 diabetes, but is already approved for other diseases (since 2008 to treat CAPS) under the name Arcalyst.  It is currently in use in about 12 phase-II and phase-III clinical trials for several different inflammation based diseases, especially Gout. It is an IL-1 inhibitor, and IL-1 is known to be involved in the destruction of beta cells in people with type-1 diabetes.  The hope is that this treatment will result in a longer, stronger honeymoon, and may result in long term improvements in A1c (such improvements might lead to fewer serious complications years or decades down the road).  This is the third treatment targeting IL-1 that I'm following. Others include Anakinra and Canakinumab.

The study will enroll 15 patients, all of who will be treated with Rilonacept (no placebo group).  To enroll you must be over 16 years old, within 5 years of diagnosis, and still producing some C-peptides (> 0.2 nmol/L) in response to food. These people will be followed for six months, involving five clinic visits, and it is hoped the trial will be complete by June 2012.  The treatment is weekly injections (under the skin, like insulin).  They will be looking for general safety issues, as well as effectiveness (A1c, C-peptides, and insulin dose).  This is NOT a honeymoon only trial, by my definition.

This is being run out of Children's Medical Center (Dallas, Texas, USA):
Principal Investigator: Perrin C White, MD    perrin.white@utsouthwestern.edu

If you are interested in participating, send Dr. White some email.  Don't worry about your C-peptide production.  If you meet the other criteria, they will test for that.

It is interesting to me how much the design of this clinical trial has changed in the last six months.  You can compare what I'm writing now, to what I wrote back then:
http://cureresearch4type1diabetes.blogspot.com/2010/06/three-new-treatments-preparing-to-enter.html
to see the differences.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00962026

Thanks very much to Dr. White for providing information about this trial.

News on the Animas Artificial Pancreas

News article on Animas's Artificial Pancreas.  Obviously, I'll be a lot more interested when it actually starts a clinical trial:
http://www.bizjournals.com/philadelphia/print-edition/2011/01/21/artificial-pancreas-awaits-fda.html

Background reading on Artificial Pancreases in General

This paper is a little dry and a little dense, but it gives a good summary update of where we are, and the lead author (Hovorka) is actively involved in AP research:
http://www.touchendocrinology.com/articles/progress-closed-loop-systems-type-1-diabetes-0?page=0%2C0

Reminder About The Blog

I'm not a doctor or research professional of any kind.  I can not provide medical advice, because I lack the knowledge.  I don't recommend one clinical trial or another.  I think that any discussion about participating in a clinical trial must be held between you and your medical team.  I know not everyone has a doctor they trust, and I'm sorry about that, but I can't give you advice on which clinical trial you should be part of, or avoid. 

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news

Three New Treatments Preparing to enter Phase-II or Phase-I Human Trials

This is a "hat trick" of new drugs preparing to enter phase-II trials for type-1 diabetes.  Each one of these has started the paperwork part of a clinical trial, but none of them have started recruiting patients as yet.  The first and last are similar anti-inflammatory drugs already approved for CAPS, while the middle is a immunosuppressive.

 
Canakinumab (ACZ885) Preparing for a Phase-II Trial
Canakinumab is a human monoclonal antibody targeted at interleukin-1 beta, and was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the US FDA and the EU EMEA in  2009. CAPS is a spectrum of autoinflammatory syndromes, and some researchers believe that inflammation is important to the type-1 diabetes process.  It is being developed by Novartis.

There is no location information in the clinical trials entry, but the responsible party is Dr. Jay S. Skyler, so I would guess Miami, Florida, USA.  The plan is to enroll 108 patients and complete in December 2014.  It is honeymooners only, you must enroll within 100 days of diagnosis.  This drug has not previously been tested on type-1 diabetes, but skips phase-I trials because it is already approved for other diseases.  It is currently in use in about 21 phase-II and phase-III clinical trials for about several different inflammation based diseases, especially Gout, Type-2 Diabetes, and Arthritis. 


clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00947427
wikipedia: http://en.wikipedia.org/wiki/Canakinumab

Alefacept Preparing for a Phase-I Trial
Alefacept is a genetically engineered immunosuppressive drug sold under the brand name Amevive was approved in 2004 for sale in Canada, the United States, Israel, Switzerland  and Australia. But not in the EU.  It is used to control inflammation  in moderate to severe psoriasis with plaque formation, where it interferes with lymphocyte activation.  Since psoriasis is an autoimmune condition broadly similar to type-1 diabetes, it is quite reasonable to try it.  However, the lack of approval in EU is worth noting; it seems to generally suppress the immune system, which can lead to side effects.  Obviously, the perfect drug would suppress the autoimmune attack on beta cells, without suppressing any other autoimmune attacks.  Usually the EU's EMEA approves new drugs (and especially new devices) more quickly than the US's FDA, but that is not the case here.


This study will be run at Emory University (Atlanta, Georgia, USA) and plans to enroll 45 patients and complete in October 2014.  It is honeymooners only, you must enroll within 6 weeks of diagnosis.  This drug has not previously been tested on type-1 diabetes, but is already approved for other diseases, as described above.  It is currently in use in about 37 phase-II, phase-III, and phase-IV clinical trials (several completed) for several diseases, especially Psoriasis.   This study is done in collaboration with Astellas Pharma US, Inc.

clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00965458
wikipedia: http://en.wikipedia.org/wiki/Alefacept

Rilonacept Preparing for a Phase-II Trial
This drug is has been available since 2008 to treat CAPS under the name Arcalyst.  It is an interleukin-1 inhibitor.

This study will be run at University of Texas Southwestern Medical Center (Dallas, Texas, USA) and plans to enroll 72 patients and complete in June 2012.  It is ultra-honeymooners only, you must enroll within 2 weeks of diagnosis.  This drug has not previously been tested on type-1 diabetes, but skips phase-I trials because it is already approved for other diseases.  It is currently in use in about 12 phase-II and phase-III clinical trials for about several different inflammation based diseases, especially Gout.


clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00962026
wikipedia: http://en.wikipedia.org/wiki/Rilonacept (but not much here)

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials