TOL-3021 Starts A Phase-II Clinical Trial

TOL-3021 causes the body to generate proinsulin so that over time the immune system will get used to (or tolerate) it.  Proinsulin and insulin are similar molecules.  Since insulin is one of the targets of the broken immune system which leads to type-1 diabetes, teaching the immune system to stop this attack may cure (or prevent) T1D.  There is other ongoing research where people are given insulin prior to the onset of T1D to try to teach the immune system not to attack insulin.  TOL-3021 takes this one step farther, by getting muscle cells to generate proinsulin over time, so the person does not need to take it repeatedly.

TOL-3021 was originally developed at Stanford University, and was then productized by Bayhills Therapeutics (where it was know as BHT-3021).  After Bayhills went out of business, development was taken over by Tolerion, Inc.

Prior to this study, this drug had been tested in an 80 person clinical trial from about 2007 to 2011.  You can read my previous blogging on TOL-3021 here:
https://cureresearch4type1diabetes.blogspot.com/search/label/TOL-3021
https://cureresearch4type1diabetes.blogspot.com/search/label/Bayhill


TOL-3021 Has Started A Phase-II Clinical Trial

This trial will enroll 50 people who are within 5 years of diagnosis.  Of those, 2/3s will be treated with TOL-3021 and 1/3 will get a placebo and be a control group.  (The previous study used weekly injections, but this study does not say exactly how often people will get the treatment.)  They will be followed for a year to measure effectiveness and then two more years for safety.  The primary end point is C-peptide production (showing an increase in insulin production).  There are also about two dozen different secondary end points covering efficiency, immunology, safety, etc.  A unique feature of the design of this trial, is that they will keep track of honeymooners separately from people with established T1D.  When the data is published, we will be able to compare how it worked on each group.

They started recruiting in July 2019, and hope to finish collecting their primary data in Aug 2021, and complete the safety follow up in 2023.

The following sites are either recruiting now, or plan to in the future:

• Stanford University California, USA, 94305 Contact: Trudy Esrey    650-498-4450    tesrey@stanford.edu  
• Chase Medical Research, LLC Hamden, Connecticut, USA, 06517 Contact: Melissa Capasso mcapasso@chasemr.com        
• Baptist Health Research Institute Jacksonville, Florida, USA, 32258  Contact: Kristy Clemmer    904-271-6363    Kristina.Clemmer@bmcjax.com               
• University of Miami Diabetes Research Institute Miami, Florida, USA, 33101-6960 Contact: Jay S Skyler, MD, MACP              
• Iowa Diabetes and Endocrinology Research Center West Des Moines, Iowa, USA, 50256 Contact: Tara Herrold    515-329-6803    therrold@iowadiabetes.com        
• Naomi Berrie Diabetes Center, Columbia University New York, New York, USA, 10032 Contact: Sarah Pollack    212-851-5425    sjp2174@columbia.edu         
• SUNY Upstate Medical University Syracuse, New York, USA, 13210 Contact: Jane Bulger    315-464-9008    bulgerj@upstate.edu        
• Mountain Diabetes and Endocrine Center Asheville, North Carolina, USA, 28803 Contact: Will Cooley    828-684-9588 ext 315    wcooley@mdecresearch.com      
• University of North Carolina Diabetes Care Center Chapel Hill, North Carolina, USA, 27517 Contact: Julie Uehling    984-974-3010    julie_uehling@med.unc.edu  
• Diabetes and Glandular Disease Clinic San Antonio, Texas, USA, 78229 Contact: Terri Ryan    210-614-8612 ext 1630    terri.ryan@dgdclinic.com  
• University of Virginia Charlottesville, Virginia, USA, 22903 Contact: Mary Voelmle    434-924-2327    MKV9F@hscmail.mcc.virginia.edu    

Registry: https://clinicaltrials.gov/ct2/show/NCT03895437

And Two More Are Preparing To Start

In addition, Tolerion has two more studies in preparation, with plans to start by the end of the year.  Both are registered with the FDA's clinical trial registry, but have not yet started recruiting.

The first is called DAWN.  It will enroll 210 people from 12 to 35 years old.  All of these people will be in the honeymoon phase of T1D.  Initially, only adults will be enrolled, but once there is enough history to show no bad side effects, they will open enrollment to younger people.  This trial will take a year to gather the data it is looking for.

The second is called DAY.  It is the same as DAWN, except that it will enroll people who have had T1D for between 1 and 5 years.  So it will exclude honeymooners, and gather data on people who have established T1D.

Tolerion's web site: https://tolerion.bio

Discussion

How Did It Work Last Time?
This trial is the follow on to a phase-I trial, so the obvious question is "how well did it work before?"  The answer is: people treated with TOL-3021 saw a 28% increase in C-peptide production, which means a 28% increase in the amount of insulin their bodies were naturally producing. (I'm reporting on "spread" here: the treated group went up about 20%, the placebo group went down about 8%, so the spread was about 28%.)

Phase-I Paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516024/

For comparison, this is similar to how well Teplizumab did in it's phase-III study, although Teplizumab did much better than that in subgroups and in earlier phase-II trials.  However, TOL-3021 had fewer side effects as compared to Teplizumab.  You can read my previous blogging on Teplizumab (and its effectiveness and safety) here:
https://cureresearch4type1diabetes.blogspot.com/search/label/Teplizumab

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.