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Type 1 Diabetes MellitusPhase 1/2TegoprubartNCT06305286

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 Phase 1/2 study testing Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy in people with Type 1 Diabetes Mellitus, run by University of Chicago at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy
Type of treatment
Injection or infusion
How many people
70 participants
Where
1 siteUnited States
Study dates
4 Mar 2024to Mar 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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;
  • 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.
  • Significant hyperlipidemia despite medical therapy defined as fasting low-density lipoprotein (LDL) cholesterol >130 mg/dL and/ or triglycerides >200 mg/dL.
  • History of any conditions that can interfere in the assessment of HbA1c due to increased red blood cell turnover or requirement for regular blood transfusions such as sickle cell disease (HbSS, hematopoietic blood stem cell (HbSC), HbS/beta thalassemia); Beta thalassemia major; Alpha Thalassemia (HbH) disease, Hemoglobin H-Constant Spring.
  • History of any other acute or chronic medical condition or pre-planned medical/surgical procedure that, in the opinion of the Principal Investigator, would compromise the safety of participants or the integrity of study results; non- compliance with recommended diabetes care in the preceding 12 months.
  • Baseline Hb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/µL), neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL). Participants with lymphopenia are allowed if the Principal Investigator determines there is no additional risk and obtains clearance from a hematologist.
  • Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) after islet cell transplantation (low-dose aspirin treatment is allowed) or participants with an international normalized ratio (INR) >1.5. The use of Plavix is allowed only when portal vein access is obtained using a mini-laparotomy procedure at the time of islet cell transplant.
  • History of factor V deficiency.
  • Administration of live attenuated vaccine(s) within 2 months of Screening.
  • Any previous treatment with Tegoprubart (AT-1501) or any other anti-CD40L therapy
  • Baseline Panel-reactive Antibody (PRA) over 20%
  • Patients with COVID-19 positive PCR tests at the time of Thymoglulin infusion.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Chicago

    Chicago, Illinois, 60637

Other trials in United States

About this study

Official title: 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

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.

Read the 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.

Being tested
Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy
Keywords
Tegoprubart, Eledon, islets, islet cell transplantation, islet transplantation, AT-1501
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapyDrug

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Day 75 and Day 365

  2. Number of Participants with graft failure post final transplant.

    Measured: Day 365

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

    Measured: at Day 365

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

    Measured: Day 28 to Day 365

  5. Number of Participants with glycosylated hemoglobin (HbA1c) <6.5%

    Measured: Day 28 through to Day 365

  6. Number of Participants free from SHEs post-first and final transplant.

    Measured: Day 28 through to Day 365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2024
  2. Study start4 Mar 2024
  3. Primary completionMar 2029 (estimated)
  4. Study completionMar 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06305286
Sponsor's protocol ID
IRB23-1367
Acronym
Tegoprubart
Status last verified
Sep 2026
First submitted
16 Feb 2024
Last updated
22 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Islet transplantation with Tegoprubart (AT-1501) immunosupression-based therapy in people with Type 1 Diabetes Mellitus, run by University of Chicago at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 22 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants who are insulin-independent post- first and final transplant (time frame: Day 75 and Day 365). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06305286.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2026.

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