Sunday, January 31, 2016

Research In The News (January)

These are a couple of old news items that I'm catching up with.

Kamada Changes Phase-II Alpha-1 Antitrypsin (AAT) Study
Kamada has announced a major change to their Phase-II trial of AAT.  Although there are several AAT trials underway, this is the farthest along, and the largest.  You can read my previous blogging here:

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.

Prior to the change: The trial would collect data on 180+ people for two years.  The first half would be double blind, but at the half way point (90 people and 1 year) the data would be analysed unblinded, to check for safety and do futility analysis.  Results from the completed trial probably would not be published until 2019, maybe longer, depending on how long recruiting took.

After the change: The 60 patients enrolled by the end of 2015 will be followed for one year, and then results will be published, probably in 2017.

What does this mean?  It means we will see results from this trial quicker than originally planned, but it also means there will be less data.  Is this good or bad?  I thought about this question quite a bit, and there are two ways to answer that question.  From my point of view, this is good, because it will mean that we have results faster.  It is true they will not be as definitive, but my gut reaction is that if there is clear good news, then it will show up even in a 60 person study.  The only danger is that with 60 people, the results will not be clear.  But my belief is that if they are not clear with 60 people, then the answer is "no".  I think it's unlikely that a drug which is so-so with 60 people is going to show as a cure with 120 or 180 people.

Of course, another question is, do these changes mean that Kamada thinks the drug is working, or do they mean Kamada thinks the drug is failing?  My answer to that is "I don't know".  The trial is double blind, so officially Kamada should not know anything about the outcome.  Even if they did, good results could motivate them to speed things up, but so could bad results (to lower expenses). I don't see a good way to "read meaning" into a shorter trial.

In the non-scientific world, it could mean that the company is running low on money, or that it is harder than expected to recruit people for the study.  As originally designed, this study would require 180+ honeymooners to enroll in one country: Israel.  That's a lot of fish to pull out of a small fishing hole.  (My very "back of the envelope" calculations suggest that about 350 people are diagnosed with type-1 in Israel per year, so you'd need to get about half of them to enroll.  If you recruited for two years then "only" 1/4 of everyone diagnosed in the entire country would need to sign up. That is hard.)

Press release:

About the inhaled version (being tested for a different disease):
AAT is already approved as an intravenous injection for treating AAT deficiency.  This is not the same type of injection as insulin; it generally requires a trip to a clinic for treatment.  However, Kamada is also testing an inhaled form to treat AAT deficiency.  If this is approved, and if AAT is found to work for type-1 diabetes, then having different forms will be convenient.  They have finished enrolling their inhaled AAT study, which is a good milestone:

Albiglutide Starts a Phase-II Trial

Albiglutide (tradenames Eperzan and Tanzeum) was approved in both the USA and the EU in 2014. It is a Byetta-like drug, designed to be used once per week, so the dosing is more like Victoza.  Like both of those drugs, Albiglutide is part of a large class of drugs called GLP-1 inhibitors.  All of these drugs are commonly used by people with type-2 diabetes.  It is not clear to me why it would cure type-1, but GlaxoSmithKline is testing it in type-1 diabetics, and it might improve A1c numbers.

This trial involves about 68 people, of whom 51 will get the drug and 17 will be in the placebo group.

The trial will take about 17 months per person.  Two months of pre-treatment screening, 12 months of treatment, and three months of post treatment monitoring.  They started in November 2014 and hope to finish by December 2016.

They will be recruiting people at about 29 different sites, in five different countries (France, UK, Germany, Italy, and Spain).  See the complete list in the clinical trial record below.

Clinical Trial Record:

My plan is to follow this study, and see if this drug turns out to be a promising treatment, a promising cure, or neither.  If it doesn't show cure potential, I will stop covering it.

If this drug does prove useful in curing (or even treating) type-1 diabetes, there are several other widely available drugs in the same category which could be tested (some are available for off label use immediately). In addition to Victoza and Byetta there are: Bydureon, Dulaglutide, and Lixisenatide.

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, January 22, 2016

Exsulin / Ustekinumab Combo Starts Phase-I Clinical Trial

Exsulin is a drug designed to trigger beta cell growth and Ustekinumab is designed to modulate the immune system.  These researchers are testing them together as a combination cure for type-1 diabetes.

My previous blogging on Exsulin (previously called INGAP) is here:
My previous blogging on Ustekinumab is here:

The Trial

The trial is on 5 people with no control group.  It started in Nov-2015 and will finish in June-2017.  It is open to adults who have had type-1 diabetes between 2 and 10 years, so this is for established type-1 diabetes, not honeymooners.  The people in the trial will get two injections of  Ustekinumab (one month apart) and twelve weeks of daily Exulin injections.

Results will be measured after six months.  The primary outcomes are "safety and tolerability" while the secondary outcomes are various C-peptide measures and one A1c measure.

This trial is recruiting at the Montreal General Hospital (Montreal, Quebec, Canada):
Contact: George M. Tsoukas, MD    514 934-8017
Contact: Louise Ullyatt, RN    514-934-1934 ext 42115


Exsulin (INGAP) is a treatment with a history.  It's gone through two major cycles of clinical trials, and neither one panned out.  The researchers think that this was because Exsulin was stimulating beta cell growth, but these new beta cells were destroyed by the autoimmune attack, so even though the Exsulin was working, it was not benefiting the patients.  They are optimistic that by pairing it with an immune modulator (Ustekinumab), patients will see the benefit.

Obviously, five people is a very small trial.  However, since these are established, adult type-1 diabetics, they should have consistently very low C-peptide numbers.  Any increase should be noticeable and would be important.

It will be interesting  to compare these results to the Ustekinumab honeymoon results.  Honeymoon is a time when the body is still naturally producing enough insulin to make a difference, so comparing Ustekinumab+honeymoon to Ustekinumab+Exsulin will tell us something about Exsulin  (or maybe effective Ustekinumab doses).  The Ustekinumab trial is scheduled to finish in March.  However, that study is still listed as recruiting and needs 20 adult honeymooners (which is a tough recruitment goal). So it might take longer than expected.

News Article:
Press Release:
Clinical Trials:

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.