Novo Nordisk and TrialNet Start TOPPLE T1D: Phase-I Trial of Four Protein Plasmid

This clinical trial is testing NNC0361-0041 which is a four protein plasmid. The drug was developed by Novo Nordisk, and the trial is being run by TrialNet. A plasmid is a bit of DNA which is not attached to the cell's main DNA.  You can think of it as a delivery service to get other molecules into a cell.  The other molecules, in this case, are four proteins: pre-proinsulin, TGF-β1, IL-10 and IL-2.  Pre-proinsulin is a chemical that is made by cells as part of the process to create insulin.  Pre-proinsulin is converted to proinsulin, which is converted to insulin.  The other three are proteins used by the immune system to communicate.  All of them have been subjects of clinical trials in the hopes they would cure/treat T1D.  So there is some appeal in the idea of using them all at once, and the plasmid is a convenient way to get all of them into cells together. 

I'm working on a blog posting which describes TrialNet, and which should come out in a month or so.

This Study

This study has a lot crammed into it.  It is the first test in people, so a phase-I trial.  However, it will enroll a total of 48 people, so closer in size to most phase-II trials.  The people will be grouped into four cohorts.  Each cohort will get a larger dose than the previous cohort, and each will have its own control group (9 treated and 3 controls per cohort).  Each cohort will be followed for a year.  The study started in Nov 2020 and they plan to finish in July 2022.

This study is open to adults (18 to 45 years old) within 4 years of T1D diagnosis; it is not limited to people in the honeymoon phase.

The primary outcome of this study is adverse events, so it is focused on safety.  However, the secondary outcome measures C-peptide, which measures how much insulin is being generated and measures progress to a cure.  The treatment will be weekly subcutaneous injections for 12 weeks.  (Subcutaneous injections are the same type as used for insulin.)

Recruiting

 

This study is recruiting all over the United States.  The entire list of recruiting sites is listed at the end of the blog.  For recruitment and enrollment related questions contact: info@trialnet.org

 

If you are a relative of someone with T1D, and want to learn about TrialNet's "Pathways to Prevention" trial, there is information here: https://trialnet.org/participate

Discussion

What really jumped out at me, was how much information they are going to get from one fairly quick study.  Normally, a phase-I trial is small.  It tests on a small number of people with a small dose.  But this study combines many of the goals of a phase-I and phase-II trial into one (especially in terms of testing multiple doses and on a total of almost 50 people).  I also like the speed of this study: less than 2 years from start of recruitment to expected results.  I just hope they are successful in recruiting enough people quickly enough to make that timeline.

While TrialNet has in the past partnered with industry to assure access to drugs, to the best of my knowledge, this is the first time TrialNet and a commercial drug company have worked together on a clinical study like this.  I think that this is an important step forward for T1D research in general. TrialNet is in a unique position to recruit people who are at-risk of T1D, but have not yet shown symptoms.  Commercial companies are well suited to develop treatments which might prevent or delay the onset of T1D.  So having these two working together plays to each of their strengths.   

Wikipedia pages:  

• Plasmid - Wikipedia 
  
• TGF beta 1 - Wikipedia
• Interleukin 10 - Wikipedia 
• Interleukin 2 - Wikipedia
• Pre-Proinsulin - Wikipedia
  

Trial Web Page:  https://www.trialnet.org/our-research/newly-diagnosed-t1d/TOPPLE
Clinical Trial Record:  Clinical Trial Record for NCT04279613

A personal note on the small size of the world:  In the 1970s, when I was a kid, I was called "little Josh".  That was because my family was friends with another family whose father was Joshua Lederburg, who we called "big Josh".  At the time, as a 10 year old, I knew that Big Josh was a smart guy who worked at Stanford University.  As it turns out, Joshua Lederburg was the scientist who named the plasmid in a paper he wrote in 1952. Six years later, he would be awarded the Nobel prize for related research.  In a sense, the clinical trial I'm reporting here is the 70 year follow on to the breakthrough he made back then.

 

List of Recruiting Sites

Stanford University
Stanford, California, United States, 94305
Contact: Trudy Esrey    650-498-4450    tesrey@stanford.edu        

Barbara Davis Center at University of Colorado Anschutz Medical Campus 

Aurora, Colorado, United States, 80045
Contact: Morgan Sooy    303-724-5686    MORGAN.QUIST@CUANSCHUTZ.EDU         

Yale University School of Medicine 

New Haven, Connecticut, United States, 06519
Contact: Laurie Feldman    203-737-2760    laurie.feldman@yale.edu        

University of Florida 

Gainesville, Florida, United States, 32610
Contact: Jennifer Hosford    352-294-5759    jennifer.hosford@peds.ufl.edu        

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, United States, 46202
Contact: Maria Spall    317-278-8879    malnicho@iu.edu         

Joslin Diabetes Center

Boston, Massachusetts, United States, 02215
Contact: Nora Bryant    617-309-4141    nora.bryant@joslin.harvard.edu        

University of Minnesota

Minneapolis, Minnesota, United States, 55466
Contact: Janice Leschyshyn    612-626-8467    lesch004@umn.edu       

The Children's Mercy Hospital 

Kansas City, Missouri, United States, 64108
Contact: Jennifer James    913-696-5059    jljames@cmh.edu        

The Naomi Berrie Diabetes Center at Columbia University Medical Center

New York, New York, United States, 10032
Contact: Sarah Pollak    212-851-5425    sjp2174@columbia.edu     

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15224
Contact: Kelli DeLallo    412-692-5210    kelli.delallo@chp.edu  

    

Benaroya Research Institute

Seattle, Washington, United States, 98101
Contact: Corinna Tordillos    206-341-8937    ctordillos@benaroyaresearch.org

 

UCSF
San Francisco, California
Contact: Karen Ko  415-514-3730  karen.ko@ucsf.edu

University of Texas Southwestern
Dallas, Texas
Contact: Lindsay Harter 214-648-4725 Lindsay.Harter@UTSouthwestern.edu

Emory University
Atlanta, Georgia
Contact: Xiaomiao Lan-Pidhainy  404-712-0051 xlanpid@emory.edu

Vanderbilt University
Nashville, Tennessee
Contact: Brenna Hammel (615) 337-9597 brenna.hammel@vumc.org

Children’s Hospital of Orange County
Orange, California
Contact: Heather Speer (714) 509-8613 hspeer@choc.org
 

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.