Current Research into Cures for Type-1 Diabetes: April 2021

Sunday, April 4, 2021

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:

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.

This blog discusses cures and preventatives for type-1 diabetes that are either in human trials or just about to start. Treatments for diabetes are not generally discussed here, unless they can turn into a cure or a preventative. My definition of a cure is this:
1. Blood sugar control without testing and with doctor's visits 4 times a year, or less. Any cure must result in an average lifespan close to normal.
2. Does not require a lifetime of immunsuppressive drugs, so it is not trading one treatment for another. (but a couple of operations, or a short course of drugs is OK)
Obviously, this is my personal definition of a cure; yours may differ.
Because a cure for type-1 diabetes is likely to involve a combination of several different drugs or treatments, I try to follow research into anything which may be an important part of the cure.

My Non-Conflict of Interest Statement

For the first 10 years of running this blog, I did not work for a company doing medical research. In 2018, I started working for Bigfoot Biomedical, which is developing an "automated insulin dosing/delivery solution" (what many call an Artificial Pancreas).
I blog on research aimed at curing type-1 diabetes, and I view Bigfoot Biomedical's work as treating type-1 diabetes (not a cure at all). Therefore, I don't view this work as conflicting with my blogging. However, if you consider the kind of automated insulin dosing/delivery solution that Bigfoot is developing to be an actual cure for type-1, then this would conflict with my blogging. I think they are quite different.
I don't get paid in any way by any company working on a cure for type-1 diabetes; I never have. And that includes free samples, free travel, or free anything. I do sometimes participate in market research studies or focus groups, and they sometimes pay.
None of the hours that I have put into my blog, or the posts that I make to any web site, has ever been paid for. (Except for some very nice and heart felt thank-you emails, and those are worth more than money.)
My daughter has type-1 diabetes and participates in clinical trials. I sometimes report on trials that she participates in, but I do not reveal her participation because I consider her medical history to be private.
I sometimes "beta test" new software or devices involved in type-1 diabetes. When I'm blogging about something where I have been given special access, I say so.
In the past I have volunteered with JDRF and The NIIB Project. I currently am a fellow with JDCA. The JDRF and NIIB work was completely unpaid. JDCA has given me equipment that I use to help my blogging, and on one occasion paid for specific consulting work.