Wednesday, October 19, 2016

Golimumab / SIMPONI Starts a Phase-II? Trial (T1GER)

Golimumab (sold as Simponi) is an immune system modulator, which has been approved in the United States and many other countries for treatment of several autoimmune diseases, so testing it on type-1 diabetes makes a lot of sense.  It has already been approved to treat rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and ankylosing spondylitis.

The Study

This study will enroll 81 people.  Half will get the treatment, and half will get a placebo, as the study is double blind.  The treatment is a subcutaneous injection once a week.  This is the same kind of injection used for insulin itself.  Everyone will be followed for two years.  The primary data will be C-peptide generation (a marker for natural insulin production), and the secondary data includes A1c, insulin usage, side effects, more C-peptide data, etc.

They started in August 2016 and plan to run until October 2019.

The researchers are planning on recruiting at 30+ different locations throughout the United States. Their clinical trials page says that right now they are only active in Atlanta, Georgia and Lexington, Kentucky. However, I do think they are actively recruiting in Walnut Creek, California as well. (People often forget to update their clinical trial record as they add more sites.)   The contact point for enrollment is this email address:


Golimumab is a monoclonal antibody (meaning it very specifically targets one type of cell). In particular, Golimumab targets TNFα (Tumor Necrosis Factor alpha) an immune signalling protein, which triggers several immune responses, including inflammation.  This is slightly controversial because researchers such as Dr. Faustman are trying to cure type-1 diabetes by increasing the levels of TNFα, while these researchers are trying to cure type-1 diabetes by decreasing the levels of TNFα. This issue came up in 2009, when Embrel (which lowers TNFα) had a mildly successful Phase-I trial. I discussed the "TNFα: Friend or Foe" at that time:

This study is being done by Janssen Research and Development, which is a large pharmaceutical company.

Clinical Trials Registry:
Drug Web Page:
Drug Wikipedia Page:
TNF  Wikipedia Page:

Joshua Levy
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.

Wednesday, October 5, 2016

JDRF Funding for a Cure 2016

In the US, we are in the "Walking Season" when JDRF asks us to walk to raise money for a cure. So I'd like to do my part, by reminding you all of how important JDRF is to the human trials of potential cures for type-1 diabetes, which I track.

Let me give you the punch line up front: 71% of the treatments currently in human trials have been funded by JDRF. (And the number is 83% for the later phase trials) This is a strong impact; one that any non-profit should be proud of. This summary does not include Artificial Pancreas research or stem cell growth trials, because there are so many of those that it would be hard to include them all.

Below is a list of all the potential cures, grouped by phase of trial that they are currently in, and separated into potential cures that JDRF has funded, and those that JDRF has never funded.

This list is a list of treatments, and many of these are being tested in more than one clinical trial.  For example, the "ATG and autotransplant" treatment is actually running three trials, but since they are all testing the same treatment, it is only one item in the list. The list below uses the following marks to show the nature of the treatments:
    (Established) One or more trials are open to people who have had type-1 diabetes for over a year.
    (Prevention) This treatment is aimed at preventing type-1 diabetes, not curing it.

Also remember that I give an organization credit for funding a treatment if they funded it at any point in development; I don't limit it to the current trial. For example, JDRF is not funding the current trials for AAT, but they did fund earlier research into it, which helped it grow into human trials. I include indirect funding of various kinds. For example, the JDRF funds nPOD,  ITN, and several other organizations, so I include research done by these other groups as well as being indirectly JDRF funded.

New This Year: Phase-II? Trials
Starting this year, I'm dividing Phase-II trials into two groups.  Phase-II trials are "classic" phase-II trials; they are done after a successful Phase-I trial in type-1 diabetes.  What I call Phase-II? trials are done with treatments which are known safe, so they don't need Phase-I trials, but have never been tested on type-1 diabetes before.  These Phase-II? trials might be Phase-II from the point of view of safety, but they are Phase-I in terms of effectiveness, so I'm putting them in their own category.

Cures in Phase-III Human Trials
Summary: currently there are no treatments aimed at curing type-1 diabetes which are in phase-III trials (under the definition of cure that I use). This is the fourth year in a row there have been no phase-III trials underway, and it's not a good thing. Even worse, I don't see a phase-III study starting even next year.  Some people might be discouraged by that, but for me, it's a reason to donate.  Money is the thing that is going to move the Phase-II studies listed below into Phase-III studies, and the Phase-I studies to Phase-II, create more Phase-I studies, and so on.

Cures in Phase-II Human Trials
Summary: there are 24 trials in phase-II, and 20 of them have been funded by JDRF, while 4 have not. Here are the treatments that have been funded by JDRF:
  • AAT (Alpha-1 Antitrypsin) by Grifols Therapeutics and also Kamada 
  • ATG and GCSF by Haller at University of Florida (Established) 
  • Abatacept by Orban at Joslin Diabetes Center 
  • Abatacept by Skyler at University of Miami (Prevention) 
  • Aldesleukin (Proleukin) at Addenbrooke’s Hospital, Cambridge, UK 
  • Diabecell by Living Cell Technologies (Established) 
  • Diamyd, Ibuprofen ("Advil"), and Vitamin D by Ludvigsson at Linköping University
  • Diamyd, Etanercep, and Vitamin D  by Ludvigsson at Linköping University
  • Diamyd and Vitamin D by Larsson at Lund University (Prevention)
  • Gleevec by Gitelman at UCSF 
  • Gluten Free Diet: Three Studies  (Preventative)
  • Oral Insulin (Preventative) 
  • Polyclonal Tregs by both Trzonkowski and Gitelman  
  • Stem Cell Educator by Zhao (Established) 
  • Teplizumab (AbATE study team) 
  • Teplizumab by Herold/Skyler/Rafkin (Prevention)
  • Tocilizumab by Greenbaum/Buckner at Benaroya Research Institute 
  • Umbilical Cord Blood Infusion by Haller at University of Florida 
  • Ustekinumab by University of British Columbia
  • Verapamil by Shalev/Ovalle at University of Alabama at Birmingham
Not funded by JDRF:
  • ATG and autotransplant by Burt, and also Snarski, and also Li 
  • BCG by Faustman at MGH (Established) 
  • Dual Stem Cell by Tan at Fuzhou General Hospital 
  • Vitamin D by Stephens at Nationwide Children's Hospital (Prevention)
Cures in Phase-II? Human Trials
Summary: there are 4 trials in phase-II, and 1 of them has been funded by JDRF, while 3 have not. Here are the treatments that have been funded by JDRF:
  • Rituximab by Pescovitz at Indiana University
Not funded by JDRF:

  • Albiglutide by GlaxoSmithKline
  • Ladarixin by  Emanuele Bosi of Dompé Farmaceutici 
  • Rapamycin Vildagliptin Combo by IRCCS (Established)
Cures in Phase-I Human Trials
Summary: there are 24 trials in phase-I, and 16 of them are funded by JDRF, while 8 are not. Here is the list funded by JDRF:
  • Alefacept by TrialNet 
  • ßAir by Beta-O2's at Uppsala University Hospital in Sweden (Established) 
  • TOL-3021 by Bayhill Therapeutics (Established) 
  • CGSF by Haller at University of Florida 
  • Trucco at Children’s Hospital of Pitt / Dendritic Cells (DV-0100) by DiaVacs (Established) 
  • Exsulin and Ustekinumab by Rosenberg at Jewish General Hospital, Canada (Established) 
  • IBC-VS01 by Orban at Joslin Diabetes Center 
  • Leptin by Garg at University of Texas 
  • Metformin by Littleford at The University of Exeter (Prevention)
  • MultiPepT1De (Multi Peptide Vaccine) by Powrie at King’s College London
  • Nasal insulin by Harrison at Melbourne Health (Prevention)
  • Smart Insulin (MK-2640) by Merck (Established) 
  • Tauroursodeoxycholic Acid (TUDCA) by Goland at Columbia University
  • Polyclonal Tregs by both Trzonkowski and Gitelman 
  • Pro insulin peptide by Dayan at Cardiff University 
  • VC-01 by Viacyte (Established)
Not funded by JDRF:
  • CGSF and autotransplant by Esmatjes at Hospital Clinic of Barcelona (Established) 
  • Encapsulated Islets at University clinical Hospital Saint-Luc (Established) 
  • Mesenchymal Stromal Cell by Carlsson at Uppsala University
  • Microvesicles (MVs) and Exosomes by Nassar at Sahel Teaching Hospital 
  • Monolayer Cellular Device (Established) 
  • Rilonacept by White at University of Texas 
  • Substance P by Vanilloid Genetics at Hospital for Sick Children Toronto (Established)
  • The Sydney Project, Encapsulated Stem Cells (Established) 
    Summary of all Trials
    52 in total
    37 funded by JDRF
    So 71% of the human trials currently underway are funded (either directly or indirectly) by JDRF. Everyone who donates to JDRF should be proud of this huge impact; and everyone who works for JDRF or volunteers for it, should be doubly proud.

    Just Looking at Trials on Established Type-1 Diabetics
    15 of these treatments (29%) are being tested on established type-1 diabetics.
    Of these, 9 are funded by JDRF
    So 60% of the trials recruiting established type-1 diabetics are funded by JDRF.

    Compared to Last Year
    In 2015 there were 42 treatments in clinical trials, in 2016 there are 52 (growth of 24%)
    In 2015 there were no treatments in Phase-III trials, in 2016 there are none (no change).
    In 2015 there were 22 treatments in Phase-II and Phase-II? trials, in 2016 there are 28 (growth of 27%).
    In 2015 there were 20 treatments in Phase-I trials, in 2016 there are 24 (growth of 20%).

    How I Count Trials for This Comparison
    • I give an organization credit for funding a cure if it funded that cure at any point in it's development cycle. 
    • I mark the start of a research trial when the researchers start recruiting patients (and if there is any uncertainty, when the first patient is dosed). Some researchers talk about starting a trial when they submit the paper work, which is usually months earlier. 
    • If there are different clinical trials aimed at proving effectiveness as a cure and as a preventative, or effectiveness in honeymooners and established diabetics, then those are counted separately. 
    • For trials which use combinations of two or more different treatments, I give funding credit, if the organization in the past funded any component of a combination treatment, or if they are funding the current combined treatment. Also, I list experiments separately if they use at least one different drug. 
    • The ITN (Immune Tolerance Network) has JDRF as a major funder, so I count ITN as indirect JDRF funding. 
    • I have made no attempt to find out how much funding different organizations gave to different research. This would be next to impossible for long research programs, anyway. 
    • Funding of research is not my primary interest, so I don't spend a lot of time tracking down details in this area. I might be wrong on details. 
    • I use the term "US Gov" for all the different branches and organizations within the United States of America's federal government (so includes NIDDK, NIAID, NICHD, etc.) 
    • I don't work for the US Gov, JDRF, or any of the other organizations discussed here. I have a more complete non-conflict of interest statement on my web site. 
    Some Specific Notes:
    • Serova's Cell Pouch and DRI's BioHub: These two clinical trials are both testing one piece of infrastructure which might be used later in a cure. They are testing a part of a potential cure. However, in both cases, the clinical trials being run now require immunosuppression for the rest of the patient's life, so I'm not counting them as testing a cure.
    • Substance P at Hospital for Sick Children Toronto: This trial is avoiding the honeymoon period by tested for insulin production.  Patients must inject more than 1/2 unit/kg to be accepted, therefore they will accept recently diagnosed people, if they are injecting enough insulin to be passed the honeymoon.  I'm counting this as "Established".
    Treatments Removed This Year:
    • Etanercept (ENBREL) by Quattrin at University at Buffalo (no movement since 2008)
    • Brod at University of Texas-Health Science Center (no movement since 2009)

    This is an update and extension to blog postings that I've made for the previous seven years:
    Finally, please remember that my blog (and therefore this posting) covers research aimed at curing or preventing type-1 diabetes that is currently being tested in humans. There is a lot more research going on, not covered here.

    Special Note: The JDRF's Role in The First Artificial Pancreas Approval by The FDA
    Although not strictly a "cure" the artificial Pancreas is clearly a huge breakthrough in diabetes treatment which will vastly lower complications, hassle, and "dead in bed" situations.  The JDRF deserves a lot of credit for getting an AP to market now.   First, the JDRF funded a lot of the basic research (and some not-so-basic research as well).   But it also helped clear the regulatory hurdles.  Even five years ago, the FDA's policies and procedures made it very difficult to get an AP approved (even one that worked well).  Simpler medical devices were approved in the EU many months before they were approved in the US.  The JDRF was instrumental in changing that.  The JDRF organized and led an informal consortium of diabetes advocates which, on the one hand, assembled scientific evidence and, on the other hand, applied grassroots political pressure which together resulted in the FDA adopting reasonable policies, and (eventually) this AP approval.

    Please think of this posting as being my personal "thank you" note to all the JDRF staff, volunteers, and everyone who donates money to research a cure for type-1 diabetes:
    Thank You!
    Finally, if you see any mistakes or oversights in this posting, please tell me! There is a lot of information packed into this small posting, and I've made mistakes in the past.

    Joshua Levy
    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.

    Saturday, October 1, 2016

    Rapamycin Vildagliptin Combo Start a Phase-II? Clinical Trial

    These researchers are running a three-armed clinical trial.  One group will get two drugs: Vildagliptin and Rapamycin.  Another group will get Rapamycin and a placebo, while a third group will get two placebos.

    Rapamycin is an immune modulator, so (I assume) it is being used to shut down the autoimmune attack. Vildagliptin is given to type-2 diabetics because it increases their insulin output.  Recent research suggests that it does this both by encouraging beta cell replication and by reducing natural beta cell death (see more discussion below).  Both of these would be valuable if Rapamycin is successful in lowering the autoimmune attack on beta cells.

    There will be 20 people in each group.  All patients will be adults (over 18 years old), who have had type-1 diabetes for five years or longer.  This is NOT a honeymoon trial.  Data will be collected over a 12 week period.  The trial started in May of 2016 and they hope to finish by December 2018.

    The primary outcome is C-peptide response (a marker for natural insulin production), and secondary outcomes include insulin use, A1c numbers, more C-peptide data, and adverse reactions.

    This trial is recruiting in Milan, Italy:
        IRCCS San Raffaele Scientific Institute
        Contact: Lorenzo Piemonti, MD    phone: 0226432706 ext +39
        Contact: Andrea Bolla, MD    phone: 0226432822 ext +39

    Clinical Trial Record:
    Wikipedia entries:


    There is a lot to like about this study.  First, the people being treated have had type-1 for a long time. Second, it's the kind of combination therapy (one drug to lower the immune attack, another to spur beta cell regrowth) that a lot of researchers have been talking about for years.  Finally, it's quick.  They will follow people for about 3 months, which means results will be available soon.  Also, the drugs are already approved for use (one in the US the other in Europe) which should make them easier to get.

    The official title for this study is "Monotherapy With Rapamycin in Long-standing Type 1 Diabetes (MONORAPA)", but I have no idea why, as it's clearly testing a combination therapy, not a monotherapy.

    I'm considering this trial to be a Phase-II? ("Phase-II previously untested") trial, because these two drugs have never been tested together for type-1 diabetes, but Rapamycin/Sirolimus alone is being actively tested in several different clinical trials, which I've blogged about before:

    Vildagliptin (sold as Galvus) is approved in Europe as a treatment for type-2 diabetes.  It is a member of a class of drugs called DPP-4 inhibitors.  More famous members of this class include Januvia and Tradjenta.  Another name for DPP-4 is CD26.

    Sirolimus (also known as Rapamycin) is an IL-2 inhibitor and immunosuppressant.  It was approved in the US in 1999 for organ rejection and cancer.

    About "Natural Cell Death"

    It's important to remember that individual cells do not last as long as people live.  Cells naturally die and new cells grow within your body all the time.  Research (mostly in animals) has suggested that Vildagliptin might have two separate effects on beta cells.  On the one hand, it seems to cause beta cells to naturally divide and grow, and on the other hand, it seems to delay beta cell's "natural death", so they live longer.    Both of these effects may be important to curing type-1 diabetes, but it is not clear.  This is why research is important.  For example, even if Vildagliptin triggers a divide-and-grow reaction, it will only be effective if there are some beta cells to start with, and we just don't know if there are enough to get things started.  On the cell death side, if the autoimmune attack directly kills beta cells, then stopping natural cell death may have little impact.  Those cells will be killed by autoimmunity before they can die of "old age".  However, if the autoimmune attack works by triggering natural cell death (which some researchers believe) then slowing natural cell death could have a large impact.

    Joshua Levy
    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.