Saturday, August 15, 2020

Update On Teplizumab

Here are three recent updates on Teplizumab.  You can read my previous summary of this drug here:https://cureresearch4type1diabetes.blogspot.com/2019/09/teplizumab-phase-ii-results-for.htmland all my Teplizumab postings here:https://cureresearch4type1diabetes.blogspot.com/search/label/Teplizumab

Updates from ADA 2020

The Teplizumab update from ADA 2020 contained several important pieces:

The average delay in onset of T1D rose from about 2 years in the previous reports, to 3 years.  This is based on following the same group of people but for a longer period of time.  My interpretation of this is that some people are simply not helped by this treatment, and they are later diagnosed with T1D.  However, for the people the treatment does help, it prevents T1D for a relatively long time, and as we follow these people for longer, that time gets longer too.  This is a good thing.

People treated with Teplizumab generated more C-peptide, in response to food, in the six months after treatment, then they had before.  This is important because usually, during this phase of the disease, C-peptide generation is slowly decreasing.  (And that was seen in the untreated group.)  C-peptide is generated by beta cells as part of their generation of insulin.  So generating more C-peptide means the beta cells are recovering or regenerating in some way.  Previous studies (in Teplizumab and other drugs) have sometimes shown preservation of insulin production by beta cells.  They stop decreasing.  But to the best of my knowledge, this is one of the few times a drug has shown increases in insulin production by beta cells in a human trial.

People in this study seemed to go through three phases: during the 6 months after treatment, their C-peptide numbers increased.  Then those numbered stayed mostly stable for months or years.  Some people continued to stay stable and were not diagnosed with T1D, while others started dropping and about 6 months after their C-peptide levels started dropping they were diagnosed with T1D.

Obviously, there are a couple of key questions that we don't know the answers to:
  1. Will repeated dosing of Teplizumab continue to delay the onset of T1D?
  2. Will dosing of Teplizumab in people with established T1D lead to increased insulin production, and therefore make their T1D easier to treat?  This study shows that increase for people who are at-risk of T1D, but we don't know about people who already have T1D.
  3. Is there are some way to know ahead of time what sort of at-risk people will be helped by this treatment, and which will not?
Great write up from JDRF / Beyond Type-1: https://beyondtype1.org/teplizumab-updates-ada-2020/
Abstracts of the two ADA 2020 presentations:

Starting A Phase-II Trial In Honeymooners

The same group that ran the successful study to see if Teplizumab could delay the onset of T1D are now running a follow-up trial.  People previously treated with Teplizumab, but who later came down with T1D, are treated again with Teplizumab to see if it has any effect on the course of their T1D.   Remember, the previous effect was to delay the onset of T1D, so now we will learn if doses after diagnosis make for a slower onset or preserve some beta cells.
This is a 30 person study.  Everyone will get the treatment and will be followed for 18 months.  No control group.  The study's primary end points are safety related, but the secondary end points include C-peptide production (showing if the body is generating its own insulin) and several other measurements.  They started in March 2020 and hope to finish in August 2024.
This study is only open to people who took part in the earlier Teplizumab study titled Teplizumab for Prevention of Type 1 Diabetes In Relatives "At-Risk"  which is TrialNet study TN-10. The contact information for this study is Provention Bio Chief Medical Officer, 908-356-0514, eramos@proventionbio.com

Ongoing PREVENT Trial

There is also the ongoing PREVENT trial of Teplizumab.  This is a phase-III study being done on honeymooners.  Due to COVID-19, they have paused recruiting new patients into this study, but when the emergency is over, they will restart recruiting.  This study needs 300 people.  You can read the study's web page here: 
and the trial registry here:


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF 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.

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Monday, August 3, 2020

Two New Clinical Trials (HCQ and Baby Teeth Stem Cells)

Hydroxychloroquine to Prevent Type 1 Diabetes

Hydroxychloroquine (HCQ) has been in the news recently because of claims that it may treat/cure COVID-19.  However, for this blog, I thought I'd update people on the clinical trials that are testing Hydroxychloroquine as a prevention of T1D.  (Note that HCQ has some T2D applications, which I'm not discussing here.)

Hydroxychloroquine is approved in the US for treatment and prevention of Malaria and some autoimmune diseases, such as Lupus and Rheumatoid Arthritis.  There are two reasons to think it might help with type-1 diabetes.  First, it helps with other autoimmune diseases.  Second, it is an anti-inflammatory and inflammation is seen in the pancreas of people with type-1 diabetes.

A large HCQ  trial started in Aug-2018 and is expected to run until Aug-2024.  The goal is to enroll 201 people who have tested positive for two autoimmune antibodies, but have not shown any symptoms of T1D.  During the study, people will take a pill, either HCQ or a placebo.  They will be followed for years to see how many are diagnosed with type-1 diabetes.  It is being run by the Type 1 Diabetes TrialNet, led by Carla Greenbaum, and JDRF is helping to fund it.

The study is double blinded, so publishing any information prior to completion in 2024 would be very difficult, and (to the best of my knowledge) no interim results have been published.

The study is recruiting people at 40 different sites all over the US.  You can read more about the study here:
the list of recruiting locations is in the Clinical Trial Registry:
to see the limitations due to COVID-19 read this:

Personal note: I know there is a lot of interest in HCQ as a COVID-19 treatment.  I have not been systematically tracking every study done in that area.  However, I can boil down what I have seen into six bullet items:
  1. In order to get a drug approved for use in the US, in normal times, there must be three high quality studies done which show safety and effectiveness (one phase-II study and two phase-III studies).
  2. Right now, there are zero high quality studies showing HCQ's impact on COVID-19.  Zero.  And that covers trials which were successful and trials which were unsuccessful.  Every trial I've seen reported, in both the scientific literature and the popular press, has been low quality.  By low quality I mean either no control group, no randomization, or it is not an intervention study at all:  very basic stuff.  I'm not quibbling about size, protocol, or even publication.
  3. There have been several low quality studies done on HCQ and COVID-19.  These studies show approximately a 1 to 2 to 1 ratio of good to bad to neutral outcomes.  So for each 4 low quality studies done, 1 has shown success (improved outcomes), 2 have shown failure (meaning higher death rates or other bad effects), and 1 has shown no difference.
  4. Because high quality research is slower and more expensive than low quality research, under normal circumstances I would never expect anyone to fund a high quality clinical trial based on the terrible results of the low quality studies done so far.  However, these are not normal circumstances, so there might be a high quality study done.  If one is done, those results will carry more weight than the stuff published so far. 
  5. Because of how clinical trials work, low quality research is far more likely to be positive than high quality research.  If you are getting unsuccessful results 3 out of 4 times with low quality results, you're not going to get successful results in higher quality studies.  That's just not the way it works.
  6. The last gasp of the true believers in a situation like this is to point at the large number of unsuccessful results, and say that they are all low quality results.  (The same is true of the small number of successful results as well, but they will not dwell on that.)  Therefore the idea is not disproven, because a high quality result would carry the day, if it were done.  Notice the switch where they are requiring mainstream science to prove their idea wrong, rather than the scientific method where new ideas must be proven correct by the proponents.  However, in real life, no one will ever do the high quality study, because the low quality studies are failing.  The true believers will blame a conspiracy, and the matter will die. 

Stem Cells From Baby Teeth Starts A Phase-I Study

This study is of personal interest to me.  My daughter was diagnosed when she was 18 months old.  When she started loosing her baby teeth it was known that each one contained a tiny amount of adult stem cells and there were companies that could freeze the teeth for later use.  At the time, little was known about how to get adult stem cells or what they could do.  But since our daughter already had T1D it seemed like something worth doing.  So we had some of her teeth preserved.   However, a few years later, there were many more known sources of adult stem cells, and the uses of adult stem cells were better known and T1D had not shown any successes with these kinds of adult stem cells.  So we stopped paying our storage fees.

Now, many years later, this is the first clinical trial I have seen that attempts to use the adult stem cells in baby teeth.

This study started in January 2019 and is expected to finish in December 2020.  It enrolled 24 people who had either T1D or T2D.  There is no control group.  Each person will get three injections of stem cells from baby teeth and then be followed for a year.  Primary outcomes are insulin usage and C-peptides (which measures how much insulin the person is creating naturally).  Secondary outcomes include A1c, blood sugar numbers, and proinsulin generation (another measure of how much insulin the person is creating naturally).


The clinical trial record contains this note, and I've never seen anything like it before: "Note: at 1 month follow-up (V5) after the last transplantation of several cells, the subjects were still unable to discontinue insulin, and then began the second course of stem cell therapy. After the second course of treatment, the follow-up plan was resumed."

My interpretation of this is that the study is fully enrolled, and that (so far) no one has been cured.  This comment seems to imply that the researchers thought they might see some outright cures in the study, and these seems very optimistic to me.


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF 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.
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