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)

Recruiting now · Phase 1/Phase 2

Conditions studied: Type 1 Diabetes Mellitus

In brief

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.

Key facts

Study ID

NCT06305286

Run by

University of Chicago

People needed

70

Starts

2024-03-04

Expected to finish

2029-03-01

Last updated by the study team

2026-03-06

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Men and women 18-65 years of age.
• A diagnosis of T1D ≥5 years with onset of disease at <40 years of age.
• Ability to provide informed consent.
• Able to comply with study procedures, including the requirement to utilize continuous glucose monitoring (CGM).
• Involvement in appropriate diabetes management in accordance with the standard of care, as directed by an endocrinologist or diabetologist with at least 4 (quarterly) clinical evaluations within the 12 months prior to Screening; using CGM*: using an insulin pump or multiple daily injection (MDI) of insulin therapy; and, unable to achieve acceptable metabolic control because of the occurrence of unexplained SHEs- at least 3 unexplained SHEs not secondary to a missed meal or dosing error, in the 12 months prior to Screening.
• CGM will be provide to subjects who otherwise qualify for study participation but have not used CGM previously.
• At least 3 unexplained SHEs not secondary to a missed meal or dosing error, in the 12 months prior to Screening.
• HbA1c level 6.5% (48 mmol/mol) to 9.5% (80 mmol/mol), inclusive.
• Absence of stimulated C-peptide (<0.3 ng/mL) in response to a 240-minute mixed- meal tolerance test (MMTT).
• Impaired awareness of hypoglycemia (IAH) as defined by a Clarke Score [Clarke 1995] of 4 or more at the time of Screening, during the Screening period, and within the last 6 months prior to the transplant.
• If female, must be surgically sterile or 2 years postmenopausal. Women of childbearing potential may be enrolled if a serum pregnancy test is negative at screening/baseline. Women of childbearing potential and men with partners that are of childbearing potential must agree to use 2 forms of highly effective methods of contraception from Screening, throughout the study, and while receiving immunosuppressive therapy for the functioning graft after the conclusion of the study. Contraception use must continue for 90 days after the last administration of the study drug (see Appendix 5). Male participants must refrain from donating sperm for the duration of the study and agree to not donate sperm for 90 days after last administration of the study drug.
• Patients with Coronavirus Disease 2019 (COVID-19) Polymerase chain reaction (PCR) negative test result at the time of Thymoglobulin infusion.

You may not qualify if…

• Any previous solid organ or islet allotransplant.
• Body mass index (BMI) >30 kg/m2.
• Weight ≤50 kg.
• Insulin requirement >1.0 unit/kg/day or <15 units/day.
• Uncontrolled proliferative diabetic retinopathy.
• Blood pressure: systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg.
• Estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation <60 mL/min/1.73 m2.
• Diagnosis of macroalbuminuria (>300 mg/g creatinine).
• For female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 90 days after discontinuation. For male participants: intent to procreate during the duration of the study or within 90 days after discontinuation or unwillingness to use effective measures of contraception.
• History of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
• History of a thromboembolic event (TE), known hypercoagulable state, or condition requiring long-term anticoagulation.
• a. Participants with a history of clotted venous access not requiring long- term anticoagulation may be included at the Principal Investigator's discretion if they have no other history of TEs or known hypercoagulable state.
• Known heparin allergy.
• Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for physiologic replacement for example in Addison disease.
• Presence of ongoing active infection including tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B, hepatitis C. Laboratory evidence of active infection even in the absence of clinical symptoms of infection is exclusionary.
• Invasive aspergillus, histoplasmosis or coccidioidomycosis infection within one year prior to Screening.
• Negative screen for Epstein-Barr Virus (EBV) by immunoglobulin G (IgG) determination.
• Current treatment with any immunosuppressive regimen, and treatment with biologic immune modulating agents, Janus kinase (JAK) inhibitors, sphingosine-1-phosphate (S1P) receptor agonists, azathioprine, Mercaptopurine (6- MP), or systemic corticosteroids in the previous 5 years.
• Persistent elevation of serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater than 3 times the upper limit of normal (ULN); elevation of total bilirubin >1.5 ULN.
• Any history of receiving experimental cell or gene therapy. Exposure to any other experimental or investigational agent within 30 days or 5 half-lives; whichever is longer.
• History of substance abuse within the past 6 months.
• Allergy to the Boost drink necessary for MMTT
• Severe cardiovascular disease characterized by any one of these conditions: a) stroke;
• b) recent myocardial infarction (within past 6 months); c) evidence of ischemia on functional cardiac exam within the last year; d) left ventricular ejection fraction <30%.
• History of significant gastrointestinal disease such as symptomatic cholecystolithiasis; acute or chronic pancreatitis; symptomatic peptic ulcer disease; severe unremitting diarrhea, vomiting or other disorders potentially interfering with the ability to absorb oral medications.

Where it is running

• University of Chicago — Chicago, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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