Three Clinical Trial Terminations: Two for Siplizumab, One for TOL-3021

Sometimes clinical trials are terminated while on going.   This is always sad for me, but it is important to keep track of the failures and also the reasons for those failures.  This blog describes three such cases.  Two are relatively recent, one fairly old, but I had not blogged on the termination before.

Phase 1b Clinical Trial of Siplizumab for T1D, Started in 2023, Terminated Due to White Blood Cell Depletion

The clinical trial, registered as NCT05574335, was an open-label, Phase 1b study designed to enroll a small group of eight participants. The trial started enrolling in 2023 and was open to individuals between 8 and 45 years of age who had been diagnosed with T1D within the previous 18 months. Participants were assigned to one of four dosing groups. The goal of the study was to identify a safe dosing regimen and to assess the effects of the treatment on residual beta cell function, with follow-up evaluations extending up to one year.

The biological being tested was Siplizumab, an investigational monoclonal antibody designed to target and selectively suppress specific immune cells, including T cells and natural killer cells. In this trial, Siplizumab was administered to participants in weekly doses for a total of 12 weeks. Prior to being evaluated in T1D, Siplizumab had undergone clinical testing as a potential treatment for psoriasis and for the prevention of acute graft-versus-host disease.

The study was initially placed on an enrollment hold and was ultimately terminated in Nov 2025 because participants experienced a greater than anticipated decrease in their white blood cell counts, a condition known as lymphodepletion.  

Clinical Trial Record: https://clinicaltrials.gov/study/NCT05574335

Phase 2 Clinical Trial of Siplizumab for New-Onset T1D, Started in 2023, Terminated for Business Reasons

The clinical trial, registered as NCT06025110, was a Phase 2, randomized, single-blind, placebo-controlled study that started in 2023. It was open to adults between 18 and 45 years of age who were recently diagnosed with T1D. The study expected to enroll 143 participants, but actually enrolled only 9.   It was designed to measure whether the treatment could preserve or improve beta-cell function. The primary endpoint evaluated the change in C-peptide levels at week 52 for patients treated with the medication compared to those receiving a placebo.

The biological being tested was TCD601, also known as Siplizumab. It is an investigational monoclonal antibody designed to selectively target and suppress the function of specific immune cells (specific T cells and natural killer cells). In this trial, the biological was administered to participants over a 12-week treatment period. Prior to this study, Siplizumab had been tested as a possible treatment for psoriasis and for the prevention of acute graft-versus-host disease, and it has also been evaluated in clinical trials for kidney and liver transplant recipients.

The trial was terminated in August 2025 due to "business reasons".  This is a few months before the study above was terminated for safety reasons.  The trial sponsor, ITB-MED, stated that the decision to halt the study was not related to any safety, efficacy, or regulatory concerns. Moving forward, ITB-MED and its strategic clinical partner, Nefro Avillion Clinical Development, will focus their resources on advancing transplant medicine, including kidney transplant induction. 

Clinical Trial Record: https://clinicaltrials.gov/study/NCT06025110

Phase 2 Clinical Trial of TOL-3021 for T1D, Initiated in 2019, Withdrawn Prior to Enrollment

The clinical trial, registered as NCT03895437 and known as the SUNRISE study, was designed as a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial. The study planned to enroll approximately 99 individuals between the ages of 12 and 41 years who had been diagnosed with T1D within the past five years.  The primary endpoint of the study was to evaluate the preservation of the body's own insulin production, measured by C-peptide levels during a four-hour mixed meal tolerance test, over a 52-week period. The trial was formally registered and initiated in March 2019 but did not proceed to the enrollment phase.

The biological treatment being evaluated was TOL-3021. It was designed to induce immune tolerance and stop the immune system from attacking insulin-producing beta cells. In this trial, TOL-3021 was intended to be administered as a weekly intramuscular injection for 52 weeks. 

The clinical trial was officially withdrawn before it enrolled its first participant, so no one was enrolled in the study. The exact reasons for the withdrawal were not published on the clinical trial registry.  Tolerion has not been active recently, so I don't expect and future work on TOL-3021.

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 BreakthroughT1D or JDCA news, views, policies or opinions. I sometimes use generative AI ("chatbots") to generate draft blogs, parts of blogs, or drafter alternate wordings for these blogs. I always review every part of every published blog to ensure that it is saying what I want, in the tone that I want, truthfully, and accurately. My kid has type-1 diabetes and has participated in clinical trials, which might be discussed here. I am obese and right on the border of T2D and therefore may be taking drugs for those conditions. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog!