Breakthrough - T1DM and Chronic Kidney Disease

NCT07592000 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB25-1433
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Single arm- subject treated with Tegoprubart and everolimus. The purpose of this research is to gather information on the safety and effectiveness of investigational regimen containing 2 experimental components:

• An investigational drug called Tegoprubart and
• Human pancreatic islet cells Both Tegoprubart and human pancreatic islet cells are considered investigational because they are not approved for use in the United States by the Food and Drug Administration (FDA). Participation in this research will last about 5 years. Assess safety, tolerability, and efficacy of transplanted islet cells and immunomodulation with Tegoprubart in combination with anti-thymocyte globulin (ATG), etanercept and with everolimus in adults with brittle T1D and chronic kidney disease (stage 2-3a).

Conditions

Diabete Type 1; Chronic Kidney Disease

Outcome Measures

Primary Outcomes (2)

• Number of participants who are achieved Optimal outcomes according to Igls criteria

  Assessed by continuous glucose monitoring (CGM) for insulin independence, HbA1c\<7.0 (53 mmol/mol), and no severe hypoglycemic episodes (SHE).

  1 year post-transplant

• Number of participants who are achieved Good outcomes according to Igls criteria

  Assessed by CGM for some insulin support, improved blood glucose control from baseline (pre-transplant), and with SHE.

  1 year post-transplant

Secondary Outcomes (7)

• Number of participants who achieved insulin independence

  1 year post-transplant, and once a year thereafter until end of study

• Number of participants with no SHE and with HbA1c ≤6.5 (48 mmol/mol)

  From 1 year post-transplant through end of study participation, assessed annually

• Number of participants with no SHE and with HbA1c ≤7.0 (53 mmol/mol)

  From 1-year post-transplant through end of study participation, assessed annually

• Number of participants with preserved renal function (maintain the same stage of CKD)

  From 1-year post-transplant through end of study participation, assessed annually

• Number of participants who developed progression of albuminuria (no albuminuria to microalbuminuria, microalbuminuria to macroalbuminuria)

  From 1-year post-transplant through end of study participation, assessed annually.

Interventions

Tegoprubart DRUG

Tegoprubart is a monoclonal antibody. Antibodies are Y-shaped proteins that are produced naturally by the 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 is thought to work by dampening down our immune system so that it will be less likely to attack the transplanted cells. For other types of transplants, like kidneys, a drug called a calcineurin inhibitor is usually used to prevent rejection. That class of drugs can be toxic to islet cells. Tegoprubart is an experimental agent that is anticipated to prevent rejection without harming the islet cells. This study will test this hypothesis.

Islet Cell Transplant BIOLOGICAL

Human pancreatic islet cells is considered investigational because it is not approved for use in the United States by the Food and Drug Administration (FDA). Participation in this research will last about 5 years. 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; performing this study will help us find if this new medication Tegoprubart, combined with either MPA or everolimus and other medication the investigators have been using routinely so far, would protect sufficiently islet transplant from the destruction by the immune system, allowing participants to stop insulin and have improved blood glucose control.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects 18-70 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, using an insulin pump or multiple daily injection (MDI) insulin therapy and, unable to achieve acceptable metabolic control because of the occurrence of unexplained SHEs.
• HbA1c level 6.5% to 9.5% inclusive.
• Absence of stimulated C-peptide (\<0.3 ng/mL) in response to a mixed- meal tolerance test (MMTT).
• Chronic kidney disease stage 1, 2 or 3a
• Impaired awareness of hypoglycemia based on:
• IAH (HypoA-Q Impaired Awareness Subscale ≥12) and at least one level 3 SHE during the last year or
• IAH and time-below-range (\<70 mg/dl) ≥4% with level 2 hypoglycemia (\<54 mg/dl) ≥1% (in Diabetes Care, Jan 2025, Patrick Choudhary) or
• Clarke Score \>4 or
• Recurrent SHE defined by two or more level 3 SHEs in the year prior to screening
• If female, must be surgically sterile or postmenopausal. Women of childbearing potential may be enrolled if a 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.

You may not qualify if:

• Body mass index (BMI) \>30 kg/m2.
• Weight ≤40 kg.
• Insulin requirement \>60units/day or \<15 units/day.
• Untreated and uncontrolled proliferative diabetic retinopathy.
• Blood pressure: systolic blood pressure (SBP) \>140 mmHg or diastolic blood pressure (DBP) \>90 mmHg.
• Chronic kidney disease stage 3b or above.
• Diagnosis of macroalbuminuria (ACR\>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:
• 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.
• Patients on aspirin are allowed.
• 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.
• Negative screen for Epstein-Barr Virus (EBV) by immunoglobulin G (IgG) determination.

Sponsors & Collaborators

• University of Chicago: lead
• Breakthrough T1D: collaborator

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Islets of Langerhans Transplantation

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Alexandra Grange - Islet Cell Transplant Program Manager

CONTACT

773-702-9771; Alexandra.Grange@bsd.uchicago.edu

Minelly Escobedo

CONTACT

Minelly.Escobedo@bsd.uchicago.edu

Study Design

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

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: May 18, 2026
• Study Start: April 29, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2030
• Last Updated: May 18, 2026

Record last verified: 2026-05

Locations

US (1)