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 it's 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 who's 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 break through 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.
As always, thanks for all the time you put into gathering and digesting this information for us. I have some concerns about how much information the NNC0361-0041 clinical trial is attempting to cover, especially in light of the fact that this is a phase-1 trial. In addition, I always find myself wishing that these clinical trials enrolled a larger number of test subjects. I guess the idea that “the larger the N, the more reliable the results” was drilled into my head a little too often during my medical training.
