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)

NCT06305286 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB23-1367
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 1 Diabetes Mellitus

Keywords

Tegoprubart; Eledon; islets; islet cell transplantation; islet transplantation; AT-1501

Outcome Measures

Primary Outcomes (1)

• Number of Participants who are insulin-independent post- first and final transplant

  Day 75 and Day 365

Secondary Outcomes (1)

• Number of Participants with glycosylated hemoglobin (HbA1c) <7.0%

  at Day 365

Other Outcomes (9)

• Number of Participants with free of serious hypoglycemic events (SHEs) post-first and final transplant

  Day 28 to Day 365

• Number of Participants with HbA1c ≤6.5% AND free from SHEs post-first and final transplant.

  at Day 365 and from Day 28 through to Day 365

• Number of Participants with graft failure post final transplant.

  Day 365

Interventions

Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy DRUG

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.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• Invasive aspergillus, histoplasmosis or coccidioidomycosis infection within one year prior to Screening.

Sponsors & Collaborators

• University of Chicago: lead
• Breakthrough T1D: collaborator
• Eledon Pharmaceuticals: collaborator
• Juvenile Diabetes Research Foundation: collaborator
• Cure Alliance: collaborator

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Related Links

• more information about the study

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Islets of Langerhans Transplantation

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Endocrine Surgical Procedures; Surgical Procedures, Operative; Transplantation

Study Officials

• Piotr Witkowski, MD PhD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Piotr Witkowski, MD PhD

CONTACT

773-702-2447; isletcelltx@bsd.uchicago.edu

Hannah Gilkey, BSN RN

CONTACT

(773) 702-2447; isletcelltx@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 12, 2024
• Study Start: March 4, 2024
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)