Eight New Stem Cell Clinical Trials For Type-1 Diabetes

I hate putting out half-digested information, but I'm convinced that I will never have time to fully digest all of these studies, so I'm putting out what I have, on the basis that something is better than nothing.

This is a list of eight studies, which are pretty similar.  They all involve using stem cells to treat or cure type-1 diabetes.  Some of these studies use adult stem cells, others embryonic, and others cord, although I think the most common is the patient's own bone marrow stem cells.

I consider stem cells to be one possible way to regenerate beta cells.  My opinion of beta cell regeneration in general, is that it is not going to cure type-1 diabetes by itself (because the autoimmune attack will kill the new beta cells same as the old ones) but that it might be an important part of the cure.  It's importance depends on how fast beta cells regrow after the autoimmune attack is stopped.  If they grow back quickly, then no form of beta regeneration will be needed, but if they grow back slowly or not at all, then some form of beta regeneration will be needed.  Stem cells are one form of beta cell regeneration, but there are others.  Exsulin and human growth hormone have been tested in people, and CureDM's drug in animals, and there are many more.

The good news here, is that there is a lot going on with stem cells, so if we do end up needing new beta cells to cure type-1 diabetes, here are 8 or more reasons why we are likely to have them.  And that is not even counting all the non-stem cell technologies out there.  But (in my opinion) the "gating factor" (what we in the software industry call the "critical path") to curing type-1 on this path is stopping the autoimmune response, not regenerating the beta cells.

As you read these, you will notice that some of them have end dates in the past, but are still active today.  Others have start dates in the past, but have not actually started recruiting patients.  These are signs that the researchers have not updated the clinical trial records, and need to.  This is quite common.  "Primary Completion" is when they finish collecting the data from the patients.

Uppsala University Hospital Stem Cell phase-I Trial
Treatment of Patients With Newly Onset of Type 1 Diabetes With Mesenchymal Stem Cells

Estimated Enrollment:	20
Study Start Date:	March 2010
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	January 2011

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT01068951


Armed Police General Hospital
Stem Cell Therapy for Type 1 Diabetes Mellitus
Cellonis Biotechnology Co. Ltd.

Estimated Enrollment:	24
Study Start Date:	August 2010
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	August 2011

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT01143168

Hospital Universitario Dr. Jose E. Gonzalez
Hematopoietic Stem Cell Transplantation in Type 1 Diabetes Mellitus

Estimated Enrollment:	15
Study Start Date:	May 2010
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	December 2010

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT01143168

Shanghai Jiao Tong University School of Medicine 
Autologous Hematopoietic Stem Cell Transplantation for Early Onset Type 1 Diabetes

Estimated Enrollment:	30
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	January 2013

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00807651

Veterens Memorial Medical Centre
Safety and Efficacy of Autologous Adipose-Derived Stem Cell Transplantation in Patients With Type 1 Diabetes
Adistem Ltd

Estimated Enrollment:	30
Study Start Date:	November 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	November 2009

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00703599

Shandong University
Autologous Bone Marrow Mononuclear Cells Transplantation in Treating Diabetes Patients

Estimated Enrollment:	200
Study Start Date:	March 2006
Estimated Study Completion Date:	March 2014

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00465478

Technische Universität München
Cord Blood Infusion for Type 1 Diabetes Mellitus (T1DM)
23 patients, but no start or end dates provided
Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00989547

University of Moron
Safety and Efficacy of Arterial Delivery of Autologous Bone Marrow Cells in the Treatment of Insulin-Dependent Diabetes
Stematix, Inc

Estimated Enrollment:	34
Study Start Date:	October 2009
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	October 2011

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00971503


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

ATG + GCSF Starts a Phase-I Clinical Trial

ATG + GCSF Starts a Phase-I Clinical Trial
This is a very interesting study, which is why I'm giving it, it's own blog posting.  The official title of this study says it all, optimistically: "Reversing Type 1 Diabetes After it is Established".  It builds on three separate lines of research: Burt's ATG/GCSF/cyclophosphamide trial, a separate line of ATG-only trials, and NOD mice trials on ATG and GCSF (all discussed more below).

The basic idea behind this research is that ATG modulates the body's immune system, while GCSG  causes the body to generate more t-cells directly from it's own bone marrow.

ATG is a mixture of different antibodies that target T cells, including the anti-CD3 antibody.  The hope is that this multi-faceted approach will be even more successful and have a longer lasting effect than with anti-CD3 alone, and may treat diabetes by several mechanisms. First, it lowers the number of T cells, so there are fewer to attack the beta cells. It also seems to alter the T cells remaining behind, rendering them less likely to be destructive. Following this depletion, the T cells that grow back in the following weeks may be reset and have a healthier balance (meaning that a special type of T cells, called regulatory T cells, will help keep the destructive T cells in check).

GCSG  is essentially a growth factor that helps the body repopulate the cells after ATG depletes them.  So, if ATG fixes the immune system by getting rid of the destructive cells, and the GCSG can cause the body to generate more t-cells afterwords, and presumably a healthier balance of these cells, then the two together could stop the autoimmune defect that causes type-1 diabetes.  (Regrowing new beta cells might still be required for some people.)  And, this process has already been used successfully to cure type-1 diabetes in mice, so that is always a good first step.

But the really positive thing about this research is it's relationship to previous research by Burt.  You can read my previous blog entries about Burt's research at the URL below, but the quick summary is this: Burt has -- by far -- the best results in people of any researcher.  That study used a combination of 3 drugs, ATG, GCSF, and cyclophosphamide.  Some patients went into remission (no need for injected insulin) for a period of years, others for months, and all of these people used much less insulin after the trial.  Only two patients in the study did not go insulin free for at least a few months.  This research also has a serious weakness, which is safety.  Although none of the people in Burt's had serious side effects, the process involves "rebooting" the immune system.  So while this is happening, the patients are in an isolation ward, because their immune system is highly compromised.  Also, there were "hints of toxicity" seen in the trial: a few people had unusual infections, and some of the males had reduced sperm counts afterward.  Burt's research was in honeymoon diabetics, only.

A second line of research that has been going for years uses ATG alone to try to preserve beta cell function in honeymoon type-1 diabetics.  This research has already completed a phase-I study, and a phase-II study is underway right now.  The phase-II study is called START and they hope to finish recruiting patients in 4-6 months.  ATG alone is very good in curing mice, but in combination with GCSF the success rate is nearly 90% for the mice, and hopefully that will translate to people.

Oversimplified a little: Burt's research involves using three drugs (ATG, GCSF, and cyclophosphamide), and reinjecting the patient's own precursor bone marrow cells (previously removed). Dosing with just ATG and GCSF can be viewed as a "kinder, gentler" Burt. Especially since the cyclophosphamide is the one that really hammers the immune system and requires the isolation ward. 

In the past, I've been asked who was following up Burt's research, and this is a pretty direct follow up. Most phase-I trials are aimed at minimum effect and maximum safety, so minimal doses are used.  The follow on research usually involves more drugs.  However, in this case the effectiveness is high, while the safety is the issue.  So the follow on research involves less drugs.  In this case it involves removing the most toxic drug from the treatment.

They are enrolling 25 people who have had type-1 diabetes for more than 4 months, but less than 2 years.  Planned completion date is April 2013.  They are recruiting at the University of Florida, which is in Gainsville.  UCSF (San Francisco, California, USA) and also the Davis Center (Denver, Colorado, USA) will be participating in this study, but they are not listed in the clinical trial record.  The coordination is through University of Florida by Dr. Michael Haller (who is running several other clinical trials aimed at type-1 as well).  The email contact is listed as hallemj@peds.ufl.edu, so I would start there if you are interested.


Previous blogging on Burt's research:  http://cureresearch4type1diabetes.blogspot.com/search/label/Burt
Previous blogging on ATG: http://cureresearch4type1diabetes.blogspot.com/search/label/ATG

Description of study: http://diabetes.ufl.edu/research/clinical-trials-and-studies/established-type-1-diabetes/atggcsf-clinical-trial/
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01106157
Abstract of animal study: http://www.ncbi.nlm.nih.gov/pubmed/19628781?dopt=Abstract
Wikipedia for GCSF: http://en.wikipedia.org/wiki/Neulasta
Wikipedia for ATG: http://en.wikipedia.org/wiki/Anti-thymocyte_globulin

I'd like to thank Dr. Steve Gitelman (who is a Principal Investigator in the ATG START study) for his thoughts on this research.  All mistakes here are my own.


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

Cinnamon and Vitamin-D

I don't usually blog on treatments for type-1 diabetes, but these two come up every now and then, and so I looked up the clinical trials for Cinnamon and also for Vitamin-D:

Studies of Cinnamon

Every now and then I hear about cinnamon helping diabetics, so I did a search for studies done on humans that gave cinnamon to people with type-1 diabetes.  There was only one.  You can read the whole paper here: http://care.diabetesjournals.org/content/30/4/813.full.pdf+html
The clinical trial record is here: http://www.clinicaltrials.gov/ct2/show/NCT00371800
Here is the important bits from the abstract (numbers removed):

RESULTS— There were no significant differences in final A1C, change in A1C, total daily insulin intake, or number of hypoglycemic episodes between the cinnamon and placebo arms.
CONCLUSIONS— Cinnamon is not effective for improving glycemic control in adolescents with type 1 diabetes.

I don't have any discussion to add to this.  One study is one study, and this one is clearly negative.

Status of Vitamin-D
There is sometimes discussion of Vitamin-D as a possible type-1 prevention or cure.  So I looked for human trials of vitamin D in people with type-1 diabetes.  I found six (listed below); two are complete, two are still recruiting, one was only looking a vascular side-effects and the last was the ongoing Haller cord blood study (where they also gave vitamin D and Omega-3s).  Below are quotes from the abstracts of the completed studies:

RESULTS: No significant differences were observed between calcitriol [vitamin-D] and nicotinamide groups in respect of baseline/stimulated C-peptide or HbA1c 1 year after diagnosis, but the insulin dose at 3 and 6 months was significantly reduced in the calcitriol [vitamin-D] group. CONCLUSIONS: At the dosage used, calcitriol [vitamin-D] has a modest effect on residual pancreatic beta-cell function and only temporarily reduces the insulin dose.

RESULTS: Safety assessment showed values in the normal range in nearly all patients, regardless of whether they received 1,25(OH)(2)D(3) [vitamin-D3] or placebo. No differences in AUC C-peptide, peak C-peptide, and fasting C-peptide after a mixed-meal tolerance test between the treatment and placebo groups were observed at 9 and 18 months after study entry, with approximately 40% loss for each parameter over the 18-month period. A1C and daily insulin requirement were similar between treatment and placebo groups throughout the study follow-up period. CONCLUSIONS: Treatment with 1,25(OH)(2)D(3) [vitamin-D3]at a daily dose of 0.25 microg was safe but did not reduce loss of beta-cell function.

So basically, one study found slight benefit and the other one found no benefit.

It is important to remember that both of these studies involved giving vitamin-D to people who already had type-1 diabetes.  Neither of these studies address the question of preventing type-1 diabetes by raising the overall level of vitamin-D prior to diagnosis.  That question is complex, and deserves it's own blog posting.  (If I have time.)  As a quick summary, I think it is fair to say that people who live nearer the equator are less likely to get type-1 diabetes than people who live nearer the poles.  Some have attributed this to the higher levels of sunlight and vitamin-D in those places, but there are many differences between people who live near the equator as compared to the poles: genetics are different, poverty is different, lifestyle is different, diet is different, etc.  So I don't find these sorts of population based studies very convincing.   A few studies which compare different populations within the same country do support the idea that vitamin-D lowers the rates of type-1 diabetes, but there are also studies that don't support this idea.   I don't think the correct answer is obvious at this time.

In general, I think it is a big mistake to compare populations in different countries (no matter what is being studied).  It is often a classic "apples vs. oranges" comparison mistake.  In the Americas (for example), this argument boils down to the idea that Canadians and Americans have a much higher type-1 diabetes rate than Mexicans.  However, there are many huge differences between Mexico and the other two countries, and to focus on vitamin-D as the cause requires more data than just the country vs. country comparison.  On the other hand, across the Atlantic the comparison boils down to high rates of type-1 diabetes in Europe compared to low rates in Africa.  Again: these are very different places!  Therefore, I do not think that comparing type-1 rates in different countries will ever provide enough support to the idea that vitamin-D has an impact on these rates.  I would limit my research to comparisons of similar populations within one country (or possibly in similar countries such as Canada vs. USA or different Nordic countries). 

Here are abstracts for the two that are complete:
http://www.ncbi.nlm.nih.gov/pubmed/16911633
http://www.ncbi.nlm.nih.gov/pubmed/20357369

Here are the clinical trial records (first two are complete, rest still recruiting):
http://www.clinicaltrials.gov/ct2/show/NCT01120119
http://www.clinicaltrials.gov/ct2/show/NCT00960635
http://www.clinicaltrials.gov/ct2/show/NCT00141986
http://www.clinicaltrials.gov/ct2/show/NCT01029392
http://www.clinicaltrials.gov/ct2/show/NCT00873925



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

Possible Cures for Type-1 in the News (late June)

Low Dose Naltrexone starts a Phase-I Trial

Background
Naltrexone was approved in 1984 for use in treating heroin addiction, but was never widely used, because of strong side effects.  The low dosage level is one tenth the dose approved, so it is much lower, and doesn't have these strong side effects. Low Dose Naltrexone (LDN) is undergoing several clinical studies aimed at different diseases.

Here is how the researchers describe this trial:

The purpose of this early study is to see if a drug called naltrexone should be studied more in people with Type I diabetes and hypoglycemia unawareness. This study will show whether naltrexone could reduce hypoglycemia unawareness. The study will also show, by using magnetic resonance imaging (also called MRI), whether naltrexone changes the way blood flows in the brain when a person is experiencing hypoglycemia.

Discussion
I'm not sure if I'm going to follow this trial as a potential cure, because it seems to be focused very specifically on "hypoglycemia unawareness", and that is not a cure.  On the other hand I mention it here, because I know that some people are very interested in Low Dose Naltrexone, and it is the first time LDN has been tried on type-1 diabetes.  Unfortunately, they are going going to be measuring blood flow in the brain, and too-low blood sugar events.  Some people think that LDN might result in lower insulin requirements, and producing more natural insulin.  However, this trial is unlikely to detect that (unless they test for more things than are mentioned in their clinical trial record). 


Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01053078
Wikipedia: http://en.wikipedia.org/wiki/Naltrexone 
Facebook group: http://www.facebook.com/group.php?v=info&gid=342192490776 


LCT's DIABCELL: Two Year Delay to General Availability

Dr. Elliot (a major player at LCT) said in a public forum:

"We do not anticipate being in the clinic before 2013 and even then in a very limited way."   Source: http://islet.org/forum/messages/53927.htm

This is a two year delay compared to their previous statement (in a yearly report) saying that they hoped to be doing transplants in Russia by 2011.

Also, LCT made a very nice presentation at ADA, which you can see here:
http://www.asx.com.au/asxpdf/20100628/pdf/31r13z624mnx7g.pdf
The really interesting slides start on page 30 and runs to the end (although slides 22 and 27 aren't bad, either).

Artificial Pancreas Photo
Here is a link to a "puff piece" in a Boston newspaper about the "bihormonal" (glucagon and insulin) AP work:
http://www.bu.edu/today/node/11148
The reason I include it is because it starts out with a big photo of a person with this AP.  Notice the five different "sets" on the person's abdomen.  It's a good reminder of where AP is and is not. How far we have come with an AP, and have far we have yet to go.

Dr. Ward's Artificial Pancreas Trials
This newspaper article describes some AP trials being done in Oregon, USA:
http://www.earthtimes.org/articles/press/an-artificial-pancreas-closer,1359773.html

These guys are testing a bihormonal (glucagon and insulin) AP device, similar to El-Khatib's group in Boston, Massachusetts, USA.  However these guys are using a different computer algorithm to control the hardware.  The key achievements include an average BG of 138 and "nighttime hypoglycemia was reduced nearly to zero".  Testing was for a 24 hour period.  I think that 21 people were involved.  (The newspaper article says "21 experiments".)

Stem Cells
I recently came across a group of 8 stem cells experiments (mostly phase-I) which did not require long term immunosupressives.  So those could be part of a future cure.  For example, if Diamyd, DiaPep, or any of the anti-CD3 treatments currently in phase-III trials pan out in honeymoon diabetics, then these stem cells might extend that cure to people with established type-1 diabetes.  I will devote a future posting to these Stem Cells trials.  With the 3 stem cell trials that I already knew about, that's 11 total. 


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

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

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

AAT (Alpha-1 Antitrypsin) Starts Phase-I 
Omni Bio announced that the Barbara Davis Center for Childhood Diabetes has received IND (Investigational New Drug) regulatory clearance from the U.S. Food and Drug Administration (FDA) to start a Phase I clinical trial evaluating Alpha-1 Antitrypsin ("AAT") in patients with type I diabetes.

This is an anti-inflammatory drug, which the body makes naturally, and which is already FDA approved for people who have a rare condition where a person don't make enough of it on their own.  You can read my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation

There is not yet a clinical trials record for this,  but the press release says they will start out with 15 people in a phase-I trial, and will try to expand to a 50 person phase-II study.  This is all being done at the Barbara Davis Center in Denver.  People in the trial will get the drug for 8 weeks, and then be followed for 2 years.  It is not clear if this will be honeymoon only, or established diabetics only, or both.

Press release: http://www.omnibiopharma.com/admin/files/file/OMBP%20IND%20CLEARANCE_JEFFERIES_FINAL%206%208%202010.pdf
Corporate web site: http://www.omnibiopharma.com/

Welcome a new treatment and a new company to the world of clinical trials to cure type-1!

Some Discussion
One of the questions that I often get asked about mice cures is "how long until this is available for people".   My stock answer is "for a new drug, at least 10 years from the start of human testing (clinical trials)".  That's a true answer, but not a complete answer, because they are usually asking right after the announcement of a successful mouse trial, but before any human trials have started.  So part of the answer is how long does it take to go from the end of animal trials to the start of human trials.

This research has taken almost exactly 2 years to make that transition from animal testing to human testing.  So that is one solid data point on how long it takes.  But remember, this drug is already FDA approved for another disease, so it is probably quicker at making the transition, than a previously unapproved drug.

One Year Delay on Dr. Faustman's Results 

In May 2010, Faustman's Lab updated their FDA clinical trial record to reflect these two new dates:
Estimated Primary Completion Date: December 2010  (Previously it had been December 2009)
Estimated Study Completion Date:  February 2011  (Previously it had been Feburary 2010)
No other updates were made.

So this represents a one year delay in completing their phase-I study.  The first date is the "data complete" date, when they hope to have gathered all the data needed for the study.  The second date is the date when everything associated with the study will be completed.  I think it is fair to say that the second date is the earliest possible publication date for the results, although the actual publication date is likely to be months after that.  The only good part of this news, is that we have already waited through a couple months of the delay, so we only have about a year to wait.  (I"m assuming that if the study is complete in February, it will get published later than same year.) 

This is only the latest in a long line of delays for Faustman's phase-I study.  It was originally expected to take 7 months and be completed in July 2008.  After a series of four delays, it is now expected to take about 37 months (if it meets it's December 2010 date).  In late 2007, they thought they were about 7 months away from data completion, and now, in mid 2010, they still think they are about 7 months away from completion.  (Actually, that's closer to 3 years without forward progress.)  One way to look at this, is that they have made no visible progress in completing their phase-I trial in the last 2+ years.

Personal opinion: I think that for any research study where delays have been over four times longer than the original total length of the study (7 months of original length vs. 30 months of delay), that study is in real trouble.  And especially, this study, which only involves studying 25 people for 3 months each.  At it's heart, it is a small, simple study, using an already approved drug.  What could cause it to take 5 times it's original length, and still not be complete?  In a future blog entry I hope to write about what could cause such a delay.  But as a "teaser," I don't see how it could be just one problem.  The worst single problem you might have might double the length of your trial, because you would have to restart from the beginning.  But this trial is about 5 times longer than initially expected.  Also, at least once, the delay occurred after recruiting was complete.  The only way that could happen is there was a problem with the data gathered, so it had to be gathered again, or if the problem was found during data analysis.

Animal Research
The Lee Iacocca foundation is now funding Kineta.  Later this year, Kineta hopes to start human trials on SK-186, which is a inflammation based treatment for type-1 diabetes.   Here is the rational for this drug:

ShK-186 is a potent and highly specific Kv1.3 potassium channel blocker. It is designed to suppress activation of effector memory T cells, which are important mediators of inflammation and tissue damage in MS, type 1 diabetes mellitus and other autoimmune diseases. The drug candidate has been shown to significantly reverse disease in animal models of MS and rheumatoid arthritis. Animal models also have demonstrated that efficacy is achieved without the generalized immunosuppression that occurs with competing therapies.

You'll notice that they don't report any success for type-1 diabetes in animal models.  As above, remember my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation


There are currently four other inflammation based cures in clinical trials (including AAT, above).  Even a few years ago, there were none at all, so this is a growth area of research.


Press release: http://www.kinetabio.com/press_releases/PressRelease03292010.pdf
Corporate web site: http://www.kinetabio.com/
 

Request for Help
I'm trying to track down information on a clinical trial of NI-0401 by NovImmune, a Swiss company.  The company is very specific that a phase-I trial has started in the Netherlands, and I've seen other references to the trial as well.  But I can not find any official record of it.  No clinical trial record, and no registered trials record, either.  Does anyone know anything about this trial?  NI-0401 is supposed to be an anti-CD3 humanized monoclonal, so much like Otelixizumab and Teplizumab.

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

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

I didn't quite get this out by the end of May, but it is the May update.....


Andromedia Starts DIA-AID2: Second phase-III Trial of DiaPep 277
Andromedia just (in April 2010) started their second phase-III trial, which will enroll 450 people and is planned to last until March 2014.  Both the EU and the US require two large scale trials for approval of new drugs, so if this study and their earlier DIA-AID trial both work well, then the approval process can start mid-2014.  It usually takes a year or two for marketing approval, so 2015 or 2016.  This treatment has only been tested on honeymoon diabetics.  

Neither this treatment nor ToleRx's (described below) will cure people by themselves.  They are both attempts to preserve some beta cells and so either extend the honeymoon or make the continuing diabetes "less brittle" in terms of fewer quick BG drops.  In both cases, I need to put together a blog posting on exactly how effective they were in their phase-II and early phase-III results.

Andromedia's DIA-AID2 page: http://www.andromedabio.com/clinical_trials.php
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01103284


ToleRx Starts DEFEND-2: Second phase-III trial of Otelixizumab
This must be the month for starting second (sometimes called "confirmatory") phase-III trials, since ToleRx is also starting one of these.  The news is just as good as Andromedia.  Actually better, since ToleRx hopes to finish their second phase-III by May 2013.  The study will have 396 people.  The same market approval math works here, so 2014 or 2015, but only if they finish their second phase-III as expected, and with the results they expect.  Both of their phase-III trials are limited to honeymooners only (so any approval would only be for newly diagnosed).  Their phase-II clinical trial (called "TTEDD") did enroll non-honeymooners.  However, it looks like good results were only seen for honeymooners (but I don't have the details handy).  That would explain why their phase-III trials are all honeymooners only.


TolerRx's DEFEND-2 page: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01123083
 

Data from XOMA Phase-I on Behcet's Disease
Previous blogging on XOMA 052: http://cureresearch4type1diabetes.blogspot.com/search/label/Xoma
Current Status on XOMA 052: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Xoma052byXoma

Behcet's Disease is an auto-inflammatory condition, which is rare in the US, but more common in Turkey.  Since XOMA 052 is an anti inflammatory, it is a natural drug to test on the disease.  It's of interest to people with type-1 diabetes because XOMA 052 is also being tested for both type-1 and type-2 diabetes (in separate phase-II trials).  Link to why inflammation might be a cause of diabetes:
http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation
(but remember that this is a minority opinion).

So, with all that a background, their results are very good (but on a very small group of people).  This trial only included 4 people.  However each person involved showed real improvement to their Behect's symptoms.

My take on this research is as follows: It shows that XOMA 052 has a major impact on inflammation in a situation similar to (but not identical with) type-1 diabetes.  So, if inflammation is a causative factor, or if reducing inflammation allows the pancreas to regrow, then XOMA 052 has a good chance of being successful.

Also, there is news about Xoma's phase-II trial in type-1 diabetics.  They have changed it considerably from the last time I looked.  It is a 24 person study, which started in Feb 2009 and is expected to finish in July 2011.  Since it lasts a year, if they finish enrollment in July 2010, then they will be on track to finish the study a year later.  This trial is open to non-honeymoon diabetics only, but there is only one site: Zurich, Switzerland.

So there are now at least two phase-II trials aimed a curing diabetes via anti-inflammatories, and they will both have results in 2011, so that might be a pivotal year for the whole idea of cures based on anti-inflammatories.

News: http://www.marketwatch.com/story/abstract-published-on-initial-results-from-xoma-052-clinical-trial-in-behcets-disease-2010-05-12?reflink=MW_news_stmp
Abstract: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=19942&ItemsPerPage=20&AppliedFilter=[SubmitterFullName]%20Like%20%27Ahmet%20%%27&ShowOnlyInFinalAcceptance=true


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.