Sunday, March 15, 2015

Tocilizumab (Actemra) Starts a Phase-II Trial

Tocilizumab (brand name: Actemra, often shortened to TCZ) blocks the action of IL-6 which is a part of the immune system. It has been approved in the USA since 2010 for use against Rheumatoid Arthritis, which, like type-1 diabetes, is an autoimmune disease.  The hope is that since it works on one autoimmune disease, it will work on another.  Usually the drug is given as an IV drip (which requires a clinic visit), but recently a subcutaneous injection was approved.  Subcutaneous injections are the same type of injection as used for insulin.

Tocilizumab Starts a Phase-II Trial

The trial is straightforward.  It is placebo controlled, double blind.  Of 108 patients in the trial, 2/3s will get the treatment and 1/3 will get the placebo.  The drug is given via IV once a month for a total of seven treatments.  The last data will be collected 2 years after the first treatment.  Researchers will gather data on C-peptide production, A1c numbers, and insulin usage.  This study is being funded by the National Institute of Allergy and Infectious Diseases (NIAID) and done in cooperation with Immune Tolerance Network (ITN), and the Diabetes TrialNet.  They are recruiting honeymoon diabetes (within 100 days of diagnosis), and expect to have ten different sites all over the US.  They hope to have results by August 2018.

The interesting part, at least to me, is how they are handling recruiting children.  They have the standard problem of recruiting honeymoon type-1 diabetics:  The FDA often requires a trial in adults before you can run a trial in children.  Of course, this is a particularly silly requirement for a drug (like Tocilizumab) which has already been approved for use in children.  In order to get around this restriction, the researchers organized their trial in the following way: The first 30 patients will all be adults.  After those adults have been treated for 12 weeks, the accumulated safety data will be reviewed, and (hopefully) the rest of the trial will be open to people of all ages.  But the downside is the delay caused by limiting recruitment to adults for about 30 out of 108 patients.  Finding adults within 100 days of diagnosis is a lot slower than finding children.

This clinical trial is currently recruiting in two locations:
Benaroya Research Institute -- Seattle, Washington, United States, 98101
    Contact: Marli McCulloch Olson    206-342-6943    marli@benaroyaresearch.org
Sanford Research -- Sioux Falls, South Dakota, USA
    Contact: Angela Vanveldhuizen    605-312-1395    angela.vanveldhuizen@sanfordhealth.org
Indiana University, Riley Hospital -- Indianapolis, IN, USA
    Contact: Bonnie Jagielo  317-278-8879  bjagielo@iu.edu

However, they are planning on adding many more sites, including these in California:
University of California San Francisco -- San Francisco, California, USA -- Rebecca Wesch 415-476-5984 weschr@peds.ucsf.edu
Stanford University  -- Stanford, California, USA -- Trudy Esrey 650-498-4450 tesrey@stanford.edu

Many more are listed in the clinical trial record.  The web site is below.

Study Web Page: http://www.extendstudy.org/
One Site's Page: https://www.benaroyaresearch.org/our-research/diabetes-clinical-research/find-study/extend-study
Clinical Trial Record: https://clinicaltrials.gov/ct2/show/NCT02293837
Wikipedia: http://en.wikipedia.org/wiki/Tocilizumab
Effect on Type-2 Diabetes: http://ard.bmj.com/content/70/6/1164.extract
(Case study were type-2 diabetics had improved A1c numbers.  Researchers assumed this was due to Tocilizumab's anti-inflammatory properties.)

Tocilizumab's safety profile is pretty good.  This study:
http://arthritis-research.com/content/13/5/r141
looked at serious adverse events and "plain old" adverse events in 8 different clinical trials run for Tocilizumab's rheumatoid arthritis approval. Five of them were phase-III trials.  You can look at the details, but basically serious adverse effects where the same in placebo, low dose and high dose.  For "plain old" adverse effects, high dose was about 10% higher than placebo, and low dose in between the two.

If Tocilizumab does prove effective, there are several other drugs available which work by blocking IL-6, and presumably they would be worth testing as well: Sarilumab, Olokizumab, and Elsilimomab are examples.

Extra Bits and Pieces

I have not found a "cured in mice" type experiment for Tocilizumab, but it has been tested in human tissue samples.  There are some mouse studies from the 1990s showing that IL-6 does effect the development of autoimmune diabetes in NOD mice.

Clinical development for this drug took about 13 years until it became available in the US, and it was first created about 25 years before commercial availability.

In 2011, the FDA approved Tocilizumab for use in children as young as two years old.

If Tocilizumab does prove effective, there are several other drugs available which work by blocking IL-6, and presumably they would be worth testing as well: Sarilumab, Olokizumab, and Elsilimomab are examples.

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.

1 comment:

Frank Sit said...

Very well written and informative article, thank you :-)

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