Iscalimab, also known by its "code name" of CFZ533 started a phase-II? trial last November, and is expected to finish in October 2022. Although it has not previously been tested on T1D, it has been tested on other diseases. A total of 11 clinical studies are either completed or currently underway, including several phase-I and phase-II trials. Iscalimab is being developed by XOMA and Novartis. It blocks a specific type of immune cell, called CD40. The drug has shown some success in clinical trials on Sjögren’s Syndrome, which is an autoimmune disease like T1D. It has also shown some success in NOD mice (which are commonly used to test potential T1D cures), although there is some controversy about this result. Iscalimab is a monoclonal antibody, which is created by cloning a single cell that attacks the cell you don't want. You end up with a vast number of identical cells, all of which attack the cell you don't want. By carefully choosing the starting cell, you can "target" the monoclonal antibody to attack a very specific type of immune cell. So if a disease is caused by a specific type of bad cell, then using a monoclonal antibody to target that type of cell is a promising treatment. This Study The study is enrolling 102 people into two groups. Two thirds will get the treatment, while one third will get a placebo and be a blinded control group. It is expected to finish in Oct-2022. The trial is open to newly diagnosed (within 2-3 months of diagnosis) children and youth (aged 6-21). The primary end points are aimed at safety (adverse events, i.e. "side effects") and effectiveness as a cure (by measuring C-peptides). There are a bunch of secondary outcomes most of which are focused on how Iscalimab moves through the body, but two are also focused on effectiveness as a cure: another C-peptide measure and a measure of people who go into partial or complete remission. The study is recruiting at three different sites in Belgium (Edegem in Antwerpen, Jette in Brussel, and Montegnee). You can contact the people running the study here: +41613241111 email@example.com or firstname.lastname@example.org Discussion One thing unique about this study is that the drug will be given in two different ways. The first dose will be given "intravenously", meaning into the vein. This generally must be done under the supervision of a medical professional. However, after the first dose, all other doses will be given "subcutaneously", meaning under the skin. This is how insulin is injected, and can be done by anyone at home. This drug has already completed 5 studies in other diseases, so its safety is well understood, which is why it has skipped a phase-I trial in people with T1D and jumped directly to a phase-II study. That is why I call this study a phase-II? study. From a safety point of view it is a phase-II study, but from an effectiveness point of view, it is a phase-I study. Iscalimab is the second T1D drug that XOMA has gotten into clinical trials. Over 10 years ago, they started a phase-II trial into Gevokizumab (Xoma 052). That was also a monoclonal antibody, but it targeted a different part of the immune system (called IL-1). It was unsuccessful. Clinical Trial: https://www.clinicaltrials.gov/ct2/show/NCT04129528 Also registered in the EU: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004553-25/BE NOD mouse results: https://link.springer.com/article/10.1007%2Fs00125-014-3342-5 Controversy in CD40 NOD mice research: https://link.springer.com/article/10.1007/s00125-019-4893-2 Genetic Result for CD40: https://academic.oup.com/jes/article/4/Supplement_1/SAT-669/5833379 News (not T1D): https://www.novartis.com/news/media-releases/novartis-presents-first-its-kind-histology-data-iscalimab-cfz533-suggesting-extended-survival-transplanted-organs-may-be-possible https://atcmeetingabstracts.com/abstract/cfz533-a-new-anti-cd40-mab-demonstrates-comparable-efficacy-and-better-renal-function-versus-tacrolimus-in-de-novo-cni-free-kidney-transplantation https://pubmed.ncbi.nlm.nih.gov/31512728/ https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(19)30135-3/fulltext 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.