Saturday, April 14, 2018

Stem Cell Educator Starts Two Phase-II Trials

The Stem Cell Educator (SCE) is an attempt to cure established type-1 diabetes by exposing a patient's immune cells to umbilical stem cells, and then returning the cells back to the patient.  Each person had a blood draw, and then a particular kind of immune cell was separated from the blood and specially processed.  The processing phase uses umbilical cord stem cells previously donated by a third party.  The patient's own "educated" immune cells were then returned to the patient.  The stem cells did not go into the person; they were only used for the external processing.

In the last six months, two new studies have started, which I blog on below.  The first is in New Jersey and the second Beijing.

The New Jersey Clinical Trial (NCT02624804)

This study will enroll 10 people.  Everyone will be treated (no control group, no blinding).
The end points are mostly safety related, but there will be some efficiency related end points as well.  There is no mention of collecting efficiency data (such as C-peptide numbers, A1c data, blood glucose, insulin usage, etc.)

This study has started recruiting.  There was hope it would start in mid 2017, but the study needed some lab infrastructure which the medical center did not have at that time, hence the delay while the new labs were set up.

Recruiting at one site: Hackensack University Medical Center
    Hackensack, New Jersey, United States, 07601
    Contact: Mariefel Vendivil    551-996-5828 
    Contact: Andrea Ortega    551-996-3923 

Clinical Trial Records:
But note that this clinical trial record is out of date.  The study has not yet started recruiting, no efficiency end points are listed, and the completion dates are too short.

The Beijing Clinical Trial (NCT03390231)

This study will enroll 100 people.  Everyone will be treated (no control group, no blinding).
The primary end point will measure specific immune cells (which are involved in type-1 diabetes) one month after treatment.  Secondary end points will cover insulin sensitivity after a month, and A1c, blood glucose, and c-peptide measurements after three months.

They started in Nov-2017, and hope to finish in either July-2018 or Dec-2020 (see discussion below).

Recruiting at one site: Department of Endocrinology, Chinese PLA General Hospital
    Beijing, China, 100853
    Contact: Yu Cheng, MD,PhD    86 10 55499301 
    Contact: Yiming Mu, MD,PhD    86 10 55499301 

Clinical Trial Records:


Differing Results: This treatment has been previously tested twice before.  One of these clinical trials had strong results, but the other one had very weak results.  I've blogged on these in the past:

The researchers believe they understand why the two trials had different results, and are hoping to apply this knowledge to the current two trials, in order to get better results.

Date confusion: The FDA's clinical trial registration page requires researchers to list three dates for a clinical trial: start date, primary completion, and study completion.  (Once the trial starts, the first is known, while the second two are estimated.)  The primary completion date is when the last data for the primary outcome will be gathered.  The study completion date is when the last data for the study will be gathered.

For the Beijing study, the primary completion date is May-2018 and the study completion date is Dec-2020.  However, the primary end point is a month after treatment, while the secondary end points are either one or three months after treatment.  So that means the study completion date should be two months after the primary completion date, not 2 1/2 years!  My guess is that there are some two year end points as well, which are not listed in the clinical trial registry.   (The New Jersey trial also has two year end points which are not listed in the registry database.)

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.

Tuesday, March 6, 2018

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

This posting is a collection of small updates.

Verapamil's Phase-II? Trial Completes Enrollment

Verapamil is a drug which has been used in the US since 1982 for high blood pressure, migraines, and heart problems.  It also lowers levels of a protein called TXNIP.  The researchers running this trial believe this is important because they believe TXNIP kills beta cells as part of the onset of type-1 diabetes.  So giving Verapamil should lower TXNIP which should improve beta cell survival, and stop type-1 diabetes.  In addition TXNIP is known to lower inflammation, and that might have an effect on type-1 diabetes as well. TXNIP worked in mice trials.

The news here is that they have completed enrollment.  There is good and bad news in that.  The good news is we now know that the trial will finish in 2019, since they completed enrollment in Jan 2018 and need to gather data for a year.  The bad news is that they only recruited 32 people; they were hoping for 52.

Clinical Trial Record:

Vitamin D Didn't Impact The Honeymoon In A Phase-I Trial

Vitamin D has been a hot topic for the last few years, and there are several different clinical trials looking at it in three different contexts: Does low Vitamin D help trigger type-1?  Does increasing Vitamin D help prevent type-1?  And, does increasing Vitamin D to people who have type-1, help treat or cure it?   All together, there are 15 completed trials, 6 recruiting, and 2 underway but not recruiting, and one not yet started.  That is strong interest.

This trial was a phase-I, honeymoon trial of 36 people.  Half got Vitamin D, and half got a placebo.  The patients who got Vitamin D did do a little better (used less insulin during their honeymoon), but the effect was not statistically significant.

Press Release:
Clinical Trial Record:

Diamyd and Vitamin D start a phase-II Trial (DIAGNODE-2)

This clinical trial will test a Diamyd injection and oral Vitamin D in honeymoon type-1 diabetes.

It is recruiting in several European countries: Czechia, Spain, and Sweden.  See the clinical trial record for a list of exact sites, there are many in each country.

Clinical Trial Record:


You can read my previous blogging on Diamyd here:

Diamyd has been tested for over 10 years.  All previous trials (which have completed) have been unsuccessful.  There are currently two other Diamyd and Vitamin D trials underway.  While I'm always hopeful that these tests will be successful, Diamyd's long history without success does not give me much to hope for with this trial.

How well can you predict the outcome of clinical trials? Not as well as you may think.

One of the guiding quotes of this blog is "Opinions are not important; but what is important is the reasoning behind them, the data and information they are built on, etc. In short: why a person has opinions is more important than the opinions themselves. And that includes my opinions. Especially "my opinions."  This is a news article on researcher's ability to predict the outcome of studies in their field.  I thought it was interesting reading:

A Stock Market Opinion: Diabetes Clinical Trials to Watch

This is a finance/stock analysis of what's important in 2018:
From my point of view, they are all type-2 focused (which makes sense from a market share point of view: type-2 is 90% of the market).

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.

Friday, February 16, 2018

Update On Two AAT Clinical Trials

This is a update on two AAT (Alpha-1 Antitrypsin) clinical trials, with a little more general summary of AAT status at the end.  AAT is an anti-inflammatory/immunomodulatory drug, which the body makes naturally, and which is already FDA approved for people who have a rare condition where they don't make enough of it on their own. Using AAT to treat type-1 diabetes is based on the idea that one of AAT's effects (lowering inflammation, immune modulation, or wound healing) can cure/prevent/treat the disease.  My previous blogging on AAT is here:

Grifols' Phase-II AAT Clinical Trial is Unsuccessful

Grifols terminated their Phase-II AAT Clinical Trial in October 2017.  "Terminated" in the sense that they ended it earlier than expected.  Their official comment was "Wk 52 primary endpoint results would be unaffected by follow-up data so trial was discontinued prior to wk 104. No safety data was collected after wk 52."  I have unofficially been told by a participant, that they were told "it was found not to be beneficial enough".

I interpret Grifols termination statement to mean: The primary results (after 52 weeks) were bad enough, so that no matter what the results from 104 weeks, it is not worth it to them to complete the trial.

In my opinion, it is morally wrong (and should be illegal), for a company to stop safety monitoring during a trial.  Even if the efficiency results are bad enough such that they don't care about that data any more, they still have a commitment to the patients in the trial to continue the promised safety monitoring.  The patients have already gotten the experimental treatment, so bad side effects or safety issues could still happen.

Clinical Trial Record:

Kamada Announces Results From Their Phase-II AAT Clinical Trial

This trial had three groups: a "low dose" group, a "high dose" group, and an untreated (placebo) group.  The primary end point was change in C-peptide generation, and secondary end points included A1c, insulin dose, and safety data.  The results have not yet been published, so I'm working off of a Kamada Press release and email interactions with the team at Kamada.  The basic results are:
  • No statistically significant results for the primary or secondary outcomes for the study as a whole (ie. "No significant treatment effect was observed in the overall study population").
  • For one subgroup (patients aged 12 to 18), there were "close to" significant results for the primary and some secondary results.  The researchers call this a "positive trend".  The full quote is "Efficacy trend was demonstrated in the pre-determined sub-group of patients between the ages of 12 to 18, treated with the higher dose of 120mg/kg.  The positive trend was observed in this age group for all three key efficacy measures of Type-1 Diabetes".
I consider this trial unsuccessful, because the primary end point was not met.  I would not consider the subgroup data to be successful either, because none of it was statistically significant.  You can read a lot more about my definition of study success here:

However, the researchers do consider it successful; successful enough to continue the work on a follow on trial aimed more specifically at the 12 to 18 year old group that had the best results here.


Differences of Opinion on Success

So, why do I think this study is unsuccessful, while the researchers think that there is a success in there, and another clinical trial will find it?  To understand this, let's look at the three results that they consider most important:
  • Better preservation of beta-cell function, as measured by less loss of C-peptide during the honeymoon (p =0.543).  
  • Lower average HbA1c and more patients with A1c below 7%  (p=0.052, p=0.048, p=0.073).
  • Lower insulin daily dose, for the higher dose treatment group versus placebo (p=0.086).
The standard cut off for statistical significance is p=0.05 or below.  So if you look at the numbers above, one is just in that range, three are close, and one is way out of range.  My view is out of range is out of range, and also the most important number (C-peptide) is not even close to an acceptable p-value.  C-peptide is most important for me, because it's the one that the FDA has previously said is the appropriate measure for curing type-1 diabetes.  A1c and insulin usage can be impacted by eating fewer carbs and having better control during the trial, but the C-peptide that they measured is inherent to how much insulin the body is producing itself.  The fact that they got the worst p-value there makes me profoundly nervous.

The researchers point out that they see good trends in three different measurements: insulin measurements, A1c, and C-peptide, and it is unlikely that you'd get three good trends in the same group of people, just by luck. P-value is designed (more or less) to show the chance that you got a good result by luck, rather than by the effectiveness of the treatment. P-values above 0.05 are considered too likely to be due to luck. However, in this case, the researchers point out, there are three different results, all of which are slightly above the cut-off. Even if one was due to luck, it is unlikely that all three would be due to luck. So the researchers look at all three together and view that as sufficiently unlikely to happen by luck, that it must be due to effectiveness. Most statisticians would look at each measurement separately, and say that each of them looked like it was due to luck, rather than effectiveness.

Since this was a phase-II trial, it was not large to begin with, and focusing on just the 12-18 year olds makes size even smaller, which is a handicap in a study like this.  Another way to view this conflict is as follows: was the clinical trial unsuccessful (poor p values) because the treatment was not effective, or was it unsuccessful (poor p values) because it was small?  Basically, if the trial were larger, would the p values have improved or would the effectiveness have diminished?

However, the path forward is the same in any case.  The researchers must do a follow on trial, which specifically recruits enough people between the ages of 12 and 18, to if the treatment is effective or not.  It is the success of that follow on study which will determine if the research continues or not.

Clinical Trial Record:
Press Release:

The Scorecard

However, there is another issue with AAT.  This is not the first data we've seen on this treatment.  Part of the reason I'm nervous about the results from this study, is that I know the results from previous studies, and none of them are particularly good.

Study Number  Phase Size Sponsor   Duration  Completion Date Results
NCT01304537     I    24  Kamada    1 year    November 2012   No strong results
NCT01319331     I    15  Omni Bio  
2 years   September 2013  No strong results

NCT01183468    II    16  NIAID     2 years   November 2014   Terminated
NCT01183455    II    66  NIAID     2 years   November 2014   Withdrawn
NCT01661192    II    12  Kamada    3 years   December 2016   Future publication
NCT02005848    II    71  Kamada    1 year    December 2017   This study
NCT02093221    II    76  Grifols   1 year    November 2017   Unsuccessful

Here is my previous blogging on the first two:

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.

Friday, February 2, 2018

University of Alberta Starts the Mozobil Phase-I Clinical Trial

Note: I'm calling this the Mozobil study, because that is the trade name of one key drug being used, and I don't have a better name for the study.  However, as described below, this study is using five different drugs.  The official title of this study is: Autologous Hematopoietic Stem Cell Mobilization (Plerixafor) and Immunologic Reset in New Onset Type 1 Diabetes Mellitus.  See why I"m going to call it the Mozobil study? :-)

This study is an attempt at "immunological reset" to cure type-1 diabetes.  The basic idea is you give one or more drugs designed to knock down the existing immune system and then one or more drugs designed to build it back up.  Since the existing immune system has the autoimmunity flaw (it attacks beta cells), the hope is the rebuilt immune system will not.

The study will start out by giving people alemtuzumab and the trio of anakinra, etanercept, and liraglutide.  The next day they will get plerixafor, and the trio, and then they will continue to get the trio of drugs for a year.
  • The alemtuzumab (sold as Campath/Lemtrada) targets one type of immune cell for destruction (CD52 cells).
  • The anakinra (sold as Kineret) and etanercept (sold as Enbrel) modulate the immune system and may lower the autoimmune attack.
  • The liraglutide (sold as Victoza) may help the body grow new beta cells.
  • The plerixafor (sold as Mozobil) encourages the body to generate new immune cells of the CD34 type.
All of these drugs are already approved in the USA and the EU for treating other diseases.

People with long memories may think this sounds familiar, and it does.  It is similar to the "Burt Brazilian Research" from 10+ years ago.   You can read my blog about it here:
and to read all my blogs about it, use this link:
You can think of this research as being a "kinder, gentler" immune system reset.   Etanercept (used in this study) has a black box warning, but nothing like the safety issues associated with cyclophosphamide (used in the earlier research).

A "black box warning" is a serious warning placed inside a black box in the FDA-mandated drug labeling.  The text will be printed on the drugs "package insert", on the FDA's web pages and on many other web pages and reference books that doctors commonly use to get information on he drugs.  (They are not printed on the label of the pill bottle, however.)  About 9% of prescription drugs have "black box warnings", and the etanercept used in this trial is one of those that has this warning.  More details are here:

The Mozobil Study

This study will enroll 60 people, and is not blinded.  Half the patients will be treated immediately, while the other half will not (thus forming a control group for the first year).  After a year, the second group of patients will be treated.  Patients must be over 18 years old, and within 6 months of diagnosis.  They hope to finish the study by Dec 2022.

They are recruiting at the University of Alberta, Edmonton, Alberta, Canada
Web site contact: May 780-407-8755
Web site contact: Cecilia 780-407-1480 contact: Andrew Malcolm, PhD    (780) 407-6952 contact: Parastoo Dinyari, BSc    (780) 407-3904 

More information:
Clinical Trial Record:

The web page has a short video.  From about the 1/2 way point to the 3/4 way point the video discusses this research:

Wikipedia entries for the drugs involved:

The primary investigator for this trial is James Shapiro, of Edmonton Protocol fame, who is also working with ViaCyte.


Comparisons To Burt
There is no question that the earlier "Burt" research has been the most successful in terms of curing type-1 diabetes.  More than half the people treated in the Burt study did not need to inject insulin for 3 or more years after treatment.  That's big.  Unfortunately, the safety issues in the Burt study were big as well.  One doctor I emailed (doing related research) felt there was an approximately 1% chance of fatality in Burt-like trials, and the treatment required a hospital isolation ward for a period of time, since the patient's immune system was so compromised.

However, this Mozobil trial does not use the highly toxic drugs used by the early Burt research.  Indeed, since all of the drugs used here are already approved for use for other diseases, we know a lot about how safe they are.  Based on the Burt research, we know that an "immune reset" can cure type-1 for a period of years.  Therefore, I can hope that we have the right combination of safety and effectiveness.

Experimental Design
The "treat half immediately and then treat the other half after a year" is a interesting experimental design that I have not seen before.  It has a couple of advantages.  First, everyone who participates will get treated.  (I know that some people don't like going through all the work of a trial, and then being in the control group and not getting the treatment.  That will not happen in this trial.)  But even though everyone will be treated, there will still be a control group for the first year, which will make it easier to see if the treatment is working or not.  Finally, the second group will be treated, but after their honeymoon phase is over.  Even though this second group will not have a control group, we will see how well this treatment works past their honeymoon phase.  Non-honeymoon diabetes is a disease that does not show spontaneous improvement over time, so it should be pretty obvious if the treatment is working, even without a placebo group.

What is a CD number (such as CD34 or CD52?)
CD stands for "cluster of differentiation", which is a unique chemical (often a protein or peptide) on the surface of a cell which is part of the immune system.  Different types of cells can have different CDs on them, and one cell can have more than one.  These CDs control how the cell interacts with other cells and are also markers which identify the cell.  For example, the CD34 marker is found only on stem cells, while the CD52 marker is found only on mature cells, and CD4 marker is found only on a specific immune cell called a "helper T-cell".

Wikipedia has more details:

Note: the researchers describe this study as a Phase-1 / Phase-2 study, and it is bigger than most Phase-I studies.  However, since I've never seen anything like it before, I'm treating it as a Phase-I study.

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.

Sunday, January 21, 2018

Diabecell Research Closes Out (With Comments on Encapsulation In General)

Diabecell is an encapsulated pig beta cell treatment aimed at curing type-1 diabetes.  This research started in the 1990s, and was part of a group of encapsulated stem cell cures which were developed at the same time by different companies/research groups.  Most of the others ended in the late 1990s and early 2000s, but LCT continued and is still operating today.  I've blogged many times on this research:

The last two running studies on Diabecell were marked as "completed" in October 2017.  The most recent clinical trial started in 2011, and published some results in 2016, but they were not strong.  Since it has been two years since their last results, and they have not started a new trial in that time, and also because the results of their trials have been lack-luster for years before that, I'm going to drop them from active coverage here.


This should serve as a cautionary tale for all encapsulated beta cell cure research.  There were at least 4 companies trying to cure type-1 diabetes this way in the 1990s, and it looks like all of those were unsuccessful.  There was another crop of these in the 2000s, and most of those have been unsuccessful as well.  (Although Viacyte, founded in 1999 as Novocell, is still in active development and may yet cure type-1 diabetes.)  More recently, in the 2010s there has been another batch of start ups in this area (Dr. Melton's Semma Therapeutics, Beta-O2 Technologies, etc.), and also an even larger batch of new academic research (such as recently reported at Cornell, UCSF, etc.)

I'm positive about all this research. I'm positive about all research aimed at curing type-1 diabetes. I hope it all works. I hope any of it works (because it only takes one cure). However, I do think it is important not to get to overly excited about encapsulated beta cell research (even as it sounds straight forward), because it's obviously more complex than it sounds.

Especially, it is clear to me that the hard part is the encapsulation part, not the beta cell part.  The pig beta cells used by LCT generate the insulin that people with type-1 diabetes injected for decades (from the 1920s to the 1970s).  Those cells work just fine, so LCT's problems are encapsulation.  Other companies have used human beta cells from cadavers.  Those cells worked just fine for their previous owners, which reinforces my belief that the breakthrough that makes encapsulated beta cells successful is going to be on the encapsulation side, not the beta cell sourcing side.

Recent Clinical Trial Records:

Academic encapsulation research in the news:

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, December 13, 2017

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

Here are some "bits and pieces" updates for December.

Update on Dr. Faustman's Phase-II Trial of BCG

Dr. Faustman's lab has published their Fall 2017 newsletter, which you can read here:
This newsletter includes more information on her research, especially from the 3rd International BCG conference, The BCG Working Group, and the 2nd edition of the BCG and Autoimmunity book she edited.

There are three pieces of new news there:
  1. The phase-II trial was fully enrolled in Summer of 2017. This is important because we now  know when the trial will end.  Since this is a five year study, they should finish collecting data in Summer of 2022 and publish before Summer of 2023. 
  2. They have given BCG to the three untreated patients from their phase-I trial, so they will have data from six people to report in the future. 
  3. The lab is going to be recruiting for more studies in the future, so would like to hear from anyone who is interested in participating.  No details on future trials were provided.
Another piece of news is that Dr. Faustman is branching out, and trying to apply BCG treatment to Fibromyalgia.  This research is being done in collaboration with EpicGenetics, and they hope to start the trial in early 2018.  If anything applicable to the type-1 world comes up in this research, I'll report it.  Since Fibromyalgia is not generally considered an autoimmune disease, I'm not sure how much "cross pollination" of results there will be.  You can read more about it here:

DILfrequency Trial Completed

There is a lot of research ongoing on IL-2 which is part of the immune system.  About 18 months ago, I summarized all this research here:
with an update here:

One of those clinical trials was called "DILfrequency" and that trial has finished, and the results published.  The purpose of that trial was to develop the best dosing method of IL-2 which could then be used in future trials.  ("Best" in this case, meant a stable and known change in the immune system, which the researchers wanted.)  It was successful in terms of telling the researchers what they wanted to know to prepare for future clinical studies.

There are several IL-2 research projects either ongoing or planned to start (including by this group), so I think we'll get a stronger signal in the next few years.

Journal Article:
Clinical Trial Record:

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.

Thursday, November 30, 2017

IMCY-0098 Starts a Phase-I Clinical Trial

I always enjoy blogging about a clinical trial for a new treatment, done by a new company, which hopes to cure type-1 diabetes. As I understand it, Imcyse, the company doing this research, has a method for creating peptides (small pieces of a protein) which will generate a type of immune cell that is able to destroy the immune cells of the body responsible for the disease. If this works, they can specifically target the cells that are causing autoimmune diseases. The company is going after Type-1 Diabetes (first), Multiple Sclerosis (second), and several other diseases after that. IMCY-0098 is the code name for their peptide targeting T1D.

IMCY-0098 Starts a Phase-I Clinical Trial

This study started in Aug 2017 and they hope to finish in Dec 2018.  They will enroll a total of 40 adult honeymooners (within 6 months of diagnosis) divided up into three groups. In addition to their regular insulin treatments, each group will get a total of 4 injections over 2 months (just below the skin, like an insulin injection).  One group will get low dose injections, one group medium dose injections, and the third group will get high dose injections; and each group will contain some controls who will get a placebo.  Patients will be followed for 6 months.  The researchers will track safety issues, effectiveness (C-peptide, A1c, etc.), and changes in the immune system.

They are currently recruiting in Belgium, Denmark, Cardiff and Oxford, and plan to start soon in France, Germany and additional location in the UK.  The list is long, and you can see the exact locations in their clinical trial record:


The company's web site includes this page:
which discusses how they are developing their treatments.  Unfortunately, it is too technical for me to understand.  But for readers with a background in immunology, this page might be valuable.

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.