Tuesday, June 12, 2018

GNbAC1 Starts A Phase-II? Trial

GNbAC1 is a monoclonal antibody which has completed phase-II testing for treating Multiple Sclerosis, which (like type-1) is an autoimmune disease.  GNbAC1 was developed by GeNeuro SA, a Swiss company, but is being tested in Australia.   They have partnered with Servier, a large French pharma company to do the phase-III trials required to bring it to the Multiple Sclerosis market.

A monoclonal antibody is an artificially created antibody which targets one very specific type of cell in the body.  Different monoclonal antibodies target different types of cells.  So if a disease is caused by a problem in one type of cell, then using a monoclonal antibody to target that type of cell is a promising treatment.  Because several monoclonal antibodies have been successful in treating other autoimmune diseases, they are an active area of research for curing type-1 diabetes.

Previously, GNbAC1 has been tested in four clinical trials as part of the Multiple Sclerosis development program, so its safety is well established (for an investigational drug).  However, since this is the first trial aimed at type-1 diabetes, I'm calling it a "Phase-II?" trial.  (The question mark meaning "no previous testing on people with type-1".)

This Study

This study has enrolled 60 people who were diagnosed with type-1 diabetes within the last 4 year.  The first part will be double blind, with 2/3s getting the treatment and 1/3 not.  After that will be a second, optional part which is not blinded (everyone will get the treatment).  Unfortunately, the primary end point for this trial is safety related.  But their press release does say that they will track various effectiveness outcomes as well (for example: C-peptide and insulin consumption).  The drug will be given as an IV drip once a month (six doses in each part of the study).  People in the study will be followed for about a year.

This study completed enrollment in January 2018, and GeNeuro plans to publish the results from the first part of the trial in September 2018, and the second part of the trial in the first half of 2019.  That is pretty quick!

Press Release: http://www.geneuro.com/data/news/GeNeuro-TD1-Study-Enrollment-Complete.pdf
Clinical Trial Registry: https://clinicaltrials.gov/ct2/show/NCT03179423
Company: http://www.geneuro.com/
General Background News Article: http://www.biotuesdays.com/features/2017/11/16/geneuro-pioneering-hervs-against-neurodegenerative-and-autoimmune-diseasess

MS research:
● http://www.msdiscovery.org/research-resources/drug-pipeline/10103-gnbac1
● https://www.ncbi.nlm.nih.gov/pubmed/25392325

Background and Rational

This clinical trial has a very different rational, as compared to previous attempts to cure type-1 with monoclonal antibodies.  In the past, these antibodies have been used to target one of the defective cell types within the immune system.  The idea is to find an immune cell which is involved in the attack on the beta cells, and kill off those immune cells.  That idea has led to some progress, some suggestive results, but nothing like a cure.

These researchers have a different idea.  They note that part of the human genome contains HERVs, which are the remains of retroviral DNA which merged into our DNA millions of years ago.  The researchers believe that while this DNA does nothing most of the time, infection can sometimes cause one of these HERVs (called "pHERV-W") to activate and generate a protein (called "pHERV-W env") used by the retrovirus the DNA came from originally.  Even after the infection, the HERV DNA stays activated.  The pHERV-W env, in turn, causes autoimmune diseases.  If true, this would explain how viral infections can "trigger" type-1 diabetes.

These researchers believe that by using a monoclonal antibody to target pHERV-W, they can stop this process.   So while previous attempts to use monoclonal antibodies targeted malfunctioning immune cells, this attempt is targeting HERV DNA which (according to this theory) is the root cause of the autoimmunity.

Background reading: https://en.wikipedia.org/wiki/Endogenous_retrovirus

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, May 20, 2018

Results from a Phase-II ATG and GCSF Combination Trial

I'm embarrassed about this blog posting, because it is very late.  It reports on news announced about 18 months ago.  I was digging through some old emails, and found it.

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

So the two of them together could make an effective combination therapy against type-1 diabetes. ATG would lower the autoimmune attack, and GCSF would help the body regrow beta cells. At least, that is the hope. I wrote about the start of this trial here, and it contains a lot of background material:

In brief: this study took 25 people, 2/3s got the treatment, and 1/3 got a placebo.  The treatment was spread out over 12 weeks.  The primary result was C-peptide results after 1 year, but this paper reported on extended results after 2 years.

Results from a Phase-II ATG and GCSF Combination Trial

The following graph is from the paper, and you can see that for the first year the treated group did noticeably better.  (Meaning they generated the same C-peptide at the end as at the beginning, while the placebo group dropped over time.)  The 3 to 6 month time period was particularly strong, with the treatment group generating more C-peptide while the control group generated less.  The first year change was statistically significant.  However, during the second year, C-peptide numbers continued to drop for both the treated and placebo groups, and the separation between the two of them shrunk, so that the difference was not statistically significant.

Research Paper:

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01106157


This is one of several studies which preserved beta cell function for a year during the honeymoon.  Early on, these studies gave me a lot of hope that they could be improved on, and eventually even lead to a cure.  However, so far I haven't seen any movement in that direction.  Treatments that preserved beta cells for one year, have (so far) not been extended to last longer.

Earlier results from this trial were strong enough so that this team started a follow on trial for honeymoon type-1s (people in their first 4 months after diagnosis):
Recruiting Site: http://www.diabetestrialnet.org/ATG-GCSF/index.htm
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02215200

There are two obvious questions in this research:
1. If this treatment were started prior to diagnosis (in people who had several autoantibodies, for example, but were not showing any symptoms of type-1 diabetes), would it prevent the onset of symptoms?
2. If this treatment were repeated on a yearly, or every two year basis, could it prevent type-1 diabetes completely?  And would the hassle and side effects of the retreating on a regular basis be worth it?

Unfortunately, the new study (in honeymooners) will not answer these questions.  But it is three times as large, so it will confirm that this study was not a fluke, and the results should be available very soon.  Recruiting was completed before July 2016, so primary data should have been collected by July 2017, and publication should be imminent.

Since this study started, there is now a new hope for this level of result ("preserving beta cells for one year").  Those results could be applied to presymptomatics: people who had two or more autoantibodies, but no symptoms of type-1.  Preserving beta cells for these people would have the effect of delaying the diagnosis of type-1 diabetes.  That would be great.  However, identifying presymptomatics to test this on has just happened in the last few years, and few studies have looked into this.  But I will be looking forward to seeing the results of these studies (as prevention).

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, April 21, 2018

250 Postings And Changes At Work

Last week's blog posting was my 250th blog posting on Current Research into Cures for Type-1 Diabetes!  Also, this year marks the 10th year of publishing the blog, as the first posting was in June 2008  (although I had created a precursor web page in 2006).

Changes At Work

In March I was laid off from my job as a software developer, so I took advantage of the impending job search to think about what I really wanted to do.  And I decided that what I really wanted was to use my software engineering skills to help the day-to-day lives of people with type-1 diabetes.

I limited my job search to companies that were working directly to make the lives of people with type-1 diabetes easier or better in some way.  I'm lucky to live and work in Silicon Valley, so there are several such companies (and non-profits) in the area.  I'm happy to say that starting in late April, I'll be starting as a "Staff Software Developer in Test" for Bigfoot Biomedical.

Several things attracted me to Bigfoot.  First, they are developing an Artificial Pancreas ("automated insulin dosing and delivery solution"), and I'm absolutely convinced that is the quickest path to better treatment, fewer complications, and an easier life for people who need insulin.  Second, their larger goal is to lower the overall burden of type-1 diabetes.   (Not just create a device that is technically better than the competition's, but to create a whole infrastructure of treatment, supplies, and support that is smooth and easy to use.)  Third, their internal software development infrastructure is cool.  It is what I'd expect from a Silicon Valley start up.

So what does this mean for the blog?

I'm not expecting any changes in the blog.  I stopped blogging on artificial pancreas research years ago, so there is no direct conflict of interest.  I won't be blogging on Bigfoot products or the products of competitors.  On the other hand, I will continue to blog about "current research aimed at curing type-1 diabetes" just as I always have.  For me, Artificial Pancreas type devices are treatments and I blog on cures, so there isn't any overlap.

I've already discussed the blog with the Bigfoot team (many are avid readers), and they are very supportive.  Bigfoot wants it's employees active in the type-1 world, and so being supportive of my blog fits into their general philosophy.

How You Can Help This Blog

There are three ways you can help this blog:
  • Tell someone about it.  I have zero budget for anything, and that includes publicity, so if you like this blog, the best way to help is to tell other people affected by type-1 about the blog.  If every reader, even just once a year, would tell one person affected by type-1 diabetes about this blog, it would reach 1000s of new readers.  And it doesn't matter if you verbally tell one person, tweet/facebook once, post to a forum or group, or send one email to one person.  It all helps.
  • If you read about research aimed at curing type-1 diabetes, which has not been discussed in the blog, then please tell me about it.  My email is below.
  • If you have questions about any blog posting or any research aimed at curing type-1 diabetes, please email your questions, or post them as comments to the blog.  These questions tell me what you care about, and they also tell me where I need to spend more time, so they are very helpful to making the blog better in the long term.
Thanks very much for all your support over all these years of blogging.

Joshua Levy 
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.

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    Mariefel.Vendivil@HackensackMeridian.org 
    Contact: Andrea Ortega    551-996-3923    Andre.Ortega@HackensackMeridian.org 

Clinical Trial Records: https://clinicaltrials.gov/ct2/show/NCT02624804
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    chengyu_301@163.com 
    Contact: Yiming Mu, MD,PhD    86 10 55499301    muyiming@301hospital.com.cn 

Clinical Trial Records: https://clinicaltrials.gov/ct2/show/NCT03390231


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: https://clinicaltrials.gov/ct2/show/NCT02372253

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: http://www.nationwidechildrens.org/medical-professional-publications/vitamin-d-and-the-honeymoon-period-of-type-1-diabetes?contentid=146302
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT01724190

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: https://clinicaltrials.gov/ct2/show/NCT03345004


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: https://clinicaltrials.gov/ct2/show/NCT02093221

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: https://www.clinicaltrials.gov/ct2/show/NCT02005848
Press Release: https://globenewswire.com/news-release/2017/11/01/1172203/0/en/Kamada-Announces-Top-line-Results-of-Phase-2-Trial-of-Alpha-1-Antitrypsin-in-Newly-Diagnosed-Type-1-Diabetes-Patients.html

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: https://en.wikipedia.org/wiki/Boxed_warning

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 qcai3@ualberta.ca
Web site contact: Cecilia 780-407-1480 chamming@ualberta.ca
Clinicaltrial.gov contact: Andrew Malcolm, PhD    (780) 407-6952    andrew.malcolm@ualberta.ca 
Clinicaltrial.gov contact: Parastoo Dinyari, BSc    (780) 407-3904    parastoo@islet.ca 

More information: http://www.islet.ca/research/mozobil
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT03182426
Alternate: https://www.1trial.com/clinicaltrials/nct03182426/stem-cell-mobilization-plerixafor-and-immunologic-reset-in-type-1-diabetes-t1dm#full_text_view

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: http://drifcan.com/drifcan-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.