NCT06305286

Safety, Tolerability, and Efficacy of Immunomodulation With A Monoclonal Antibody Against CD40L in Combination With Transplanted Islet Cells in Adults With Brittle Type 1 Diabetes Mellitus (T1D)

A Pilot Study Assessing the Safety of Using a Monoclonal Antibody Against Cluster of Differentiation 40 (CD40) Ligand to Achieve a Calcineurin Inhibitor-free Immunosuppression Regimen in Patients With Type 1 Diabetes Mellitus (T1D) and Problematic Hypoglycemia Undergoing Islet Cell Transplantation

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Tegoprubart (AT-1501) is a monoclonal antibody. Antibodies are Y-shaped proteins that are produced naturally by the subject's immune system to attack and fight foreign substances that cause illness. Monoclonal antibodies are man-made proteins manufactured to serve as substitute antibodies to fight diseases. Monoclonal antibodies can restore, enhance, or mimic (copy) the immune system's attack process; they can also tone down the immune system. Tegoprubart (AT-1501) is thought to work by dampening down the immune system so that it will be less likely to attack the transplanted cells. For other types of transplants, like kidney, a drug called a calcineurin inhibitor is usually used to prevent rejection. That class of drugs can be toxic to islet cells. Tegoprubart (AT-1501) is an experimental agent that is anticipated to prevent rejection without harming the islet cells.

Detailed description

By doing this study, the study team is studying an investigational regimen containing 2 experimental components: * An investigational drug called AT-1501 and * Human pancreatic islet cells Both Tegoprubart (AT-1501) and human pancreatic islet cells are considered investigational because they are not currently approved for use in the United States. Islet cells are the specialized cells in the pancreas that produce insulin. In this study, islet cells will be collected from the pancreas of a deceased organ donor and transplanted into the body. The goal of this study is to see whether these transplanted islet cells can take over insulin production. The study team will evaluate how well the subject makes insulin and how well-controlled blood sugar is after the transplant. The islet transplant procedure involves inserting a thin, flexible tube called a catheter through a small cut in the upper abdomen. A radiologist uses X-rays and ultrasound to guide the catheter into the portal vein of the liver where the islet cells are delivered. This study of islet transplantation will test to see if islet transplantation is safe and effective. Because these islet cells come from another person, the subject's immune system may recognize them as foreign and attack them. Standard immunosuppressive medicines (Anti-thymocyte globulin \[ATG\] or Basiliximab, mycophenolate mofetil/mycophenolate sodium (MMF/MPS) (CellCept®), and Etanercept) will be used to help prevent the body from attacking the transplanted islet cells. Tegoprubart (AT-1501) will be given in combination with these standard immunosuppressive medicines to test whether the investigational drug is safe, tolerable, and efficacious. The effect of the combination of Tegoprubart (AT-1501) with other immunosuppressant medications has not been previously tested.

Conditions

• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy	Tegoprubart (AT-1501) is a monoclonal antibody for Injection is a humanized immunoglobulin G1 (IgG1) kappa monoclonal anti-CD40L antibody that blocks CD40L binding to its receptor, CD40. Safety and effectiveness of islet transplantation with Tegoprubart- based, calcineurin inhibitor-free (tacrolimus-free) immunosupression regimen is being tested. The goal is improve outcomes of islet transplantation avoiding toxicity and side effect of standard, tacrolimus- based immunosupression therapy.

Timeline

• Start date: 2024-03-04
• Primary completion: 2029-03-01
• Completion: 2029-03-01
• First posted: 2024-03-12
• Last updated: 2026-03-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study