AT-1501 + Islet Cell Transplant for Type 1 Diabetes

Overseen By Piotr Witkowski, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must be taking: Insulin

Must not be taking: Systemic steroids, Immunosuppressants

Disqualifiers: Obesity, Hypertension, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AT-1501, a lab-made protein that may prevent the body from rejecting transplanted islet cells in people with Type 1 Diabetes. Islet cells help control blood sugar, and the trial aims to determine if AT-1501 can protect these cells without causing harm. Suitable candidates for this trial include those who have had Type 1 Diabetes for at least 5 years, frequently experience severe, unexplained low blood sugar episodes, and use a continuous glucose monitor or insulin pump. As a Phase 1, Phase 2 trial, this research focuses on understanding how AT-1501 works in people and measuring its effectiveness in a smaller group, offering participants a chance to be among the first to benefit from this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently on certain treatments like systemic steroids or immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that AT-1501 is likely to be safe for humans?

Research has shown that AT-1501, a monoclonal antibody, has shown promise in animal studies. These studies found it helps transplanted islet and kidney cells survive without causing harm. For people with Type 1 diabetes, early findings suggest AT-1501 could be a safer option compared to other drugs that might damage islet cells. In another study with people who have Type 1 diabetes, initial results were positive, and no major safety issues were reported. This suggests that AT-1501 is well-tolerated in early human research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Type 1 Diabetes, which often involves insulin therapy and continuous glucose monitoring, AT-1501 offers a novel approach by targeting the CD40 ligand pathway. This mechanism is intended to modulate the immune response, potentially reducing the body's attack on transplanted islet cells. Researchers are excited about AT-1501 because it might enhance the success of islet cell transplants, offering a more sustainable way to manage blood sugar levels and reducing dependence on insulin. This innovative strategy could lead to longer-lasting transplants and better overall outcomes for individuals with Type 1 Diabetes.

What evidence suggests that AT-1501 might be an effective treatment for Type 1 Diabetes?

Research has shown that AT-1501, also known as Tegoprubart, might help the body accept transplanted islet cells without causing harmful side effects. Studies in animals, such as monkeys, demonstrated that AT-1501 helps these transplanted cells survive and function effectively by calming the immune system, reducing the risk of the body attacking the new cells. Early results from human studies suggest that patients using AT-1501 required less insulin and experienced better outcomes compared to those using traditional drugs. This treatment is promising because it aims to prevent rejection without harming the transplanted cells. ^{1 2 3 4 6}

Who Is on the Research Team?

John Fung, MD PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults aged 18-65 with brittle Type 1 Diabetes Mellitus, diagnosed for over 5 years and onset before age 40. Participants must have had at least three severe hypoglycemic episodes in the past year not due to missed meals or dosing errors, an HbA1c level between 7.0% and 9.5%, no C-peptide response after a meal test, impaired awareness of hypoglycemia, and be under regular diabetes management.

Inclusion Criteria

Patients with Coronavirus Disease 2019 (COVID-19) Polymerase chain reaction (PCR) negative test result

Ability to provide informed consent

Able to comply with study procedures, including the requirement to utilize continuous glucose monitoring (CGM)

Exclusion Criteria

Blood pressure: systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg

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

Baseline Panel-reactive Antibody (PRA) over 20%

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Islet Cell Transplantation

Participants undergo islet cell transplantation using a catheter guided by X-rays and ultrasound

1 week

1 visit (in-person)

Treatment

Participants receive AT-1501 in combination with standard immunosuppressive medicines to prevent rejection of transplanted islet cells

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AT-1501

Trial Overview The trial is testing AT-1501, a man-made antibody designed to suppress the immune system without harming transplanted islet cells that produce insulin. This could help prevent the body from rejecting these cells in patients with T1D who receive cell transplants to manage their condition.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Cure Alliance

Collaborator

Trials

1

Recruited

9+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Published Research Related to This Trial

A chimeric CD40-specific monoclonal antibody (Chi220) was effective in promoting the survival of transplanted neonatal porcine islets in diabetic macaques, with five out of six recipients achieving insulin independence for a median of 59 days.

This study suggests that targeting the CD40 pathway may be a promising alternative to the CD154 pathway for improving islet xenotransplantation outcomes, with no observed thromboembolic complications, indicating a potentially safer approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD40-specific costimulation blockade enhances neonatal porcine islet survival in nonhuman primates. Thompson, P., Cardona, K., Russell, M., et al.[2023]

The monoclonal antibody AT-1501 (Tegoprubart) effectively promotes long-term survival of islet and kidney transplants in nonhuman primate models, demonstrating its potential as a safe immunosuppressive agent.

AT-1501 treatment resulted in improved metabolic outcomes, such as higher C-peptide levels and weight gain, along with a lower incidence of cytomegalovirus reactivation compared to traditional immunosuppressive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates. Anwar, IJ., Berman, DM., DeLaura, I., et al.[2023]

In a study involving diabetic rhesus macaques, the combination of CTLA4Ig with a CD40 blockade regimen led to long-term survival of transplanted islets and was well tolerated, indicating its potential as a safer immunosuppressive strategy.

The addition of CTLA4Ig effectively prevented the formation of donor-specific antibodies (DSA), which are a major barrier to successful islet transplantation, suggesting that this approach could improve outcomes in clinical settings without relying on traditional CD154 blockade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA4Ig prevents alloantibody formation following nonhuman primate islet transplantation using the CD40-specific antibody 3A8. Badell, IR., Russell, MC., Cardona, K., et al.[2023]

The human CD40-specific monoclonal antibody (mAb) 3A8 significantly prolonged islet allograft survival in a rhesus macaque model without depleting B cells, suggesting its potential as a safer alternative for preventing transplant rejection.

Unlike previous strategies that relied on blocking CD154, the efficacy of 3A8 indicates that complete blockade of CD40 binding or cellular depletion is not necessary for effective allograft protection, paving the way for further development of CD40-targeted therapies in human transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nondepleting anti-CD40-based therapy prolongs allograft survival in nonhuman primates. Badell, IR., Thompson, PW., Turner, AP., et al.[2023]

The novel monoclonal antibody 2C10 effectively inhibited T cell-dependent antibody responses in rhesus macaques without causing significant depletion of peripheral B cells, indicating a safer immunosuppression strategy.

In a transplantation model, 2C10 significantly prolonged islet graft survival compared to standard treatments, highlighting its potential as an effective therapy for preventing alloimmune responses in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel monoclonal antibody to CD40 prolongs islet allograft survival. Lowe, M., Badell, IR., Thompson, P., et al.[2023]

ASKP1240, a fully human anti-CD40 monoclonal antibody, significantly prolonged the survival of pancreatic islet transplants in cynomolgus monkeys, with graft survival times extending beyond 600 days compared to control groups that rejected transplants within 9 days.

The treatment with ASKP1240 did not result in serious adverse events and effectively abolished anti-donor cellular responses and antibodies, suggesting it could be a safe and effective option for immunosuppression in clinical islet transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ASKP1240, a fully human anti-CD40 monoclonal antibody, prolongs pancreatic islet allograft survival in nonhuman primates. Watanabe, M., Yamashita, K., Suzuki, T., et al.[2023]

Citations

1. ir.eledon.com ir.eledon.com/news-releases/news-release-details/eledon-pharmaceuticals-announces-positive-initial-data-subjects

Eledon Pharmaceuticals Announces Positive Initial Data ... Eledon Pharmaceuticals Announces Positive Initial Data from Subjects with Type 1 Diabetes Treated with Tegoprubart as Part of an ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10990482/

The anti-CD40L monoclonal antibody AT-1501 promotes islet ... These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in non-human primate models.

3. breakthrought1d.org breakthrought1d.org/grants/united-states/illinois/a-pilot-study-assessing-the-safety-of-using-a-monoclonal-antibody-against-cd40-ligand-to-achieve-a-calcineurin-inhibitor-free-immunosuppression-regimen-in-patients-with-type-1-diabetes-mellitus-t1d/

A pilot study assessing the safety of using a monoclonal ... Tegoprubart (also known as AT-1501) is an experimental agent being studied in islet cell transplant recipients. Type 1 diabetes (T1D) is a lifelong disease that ...

4. ir.eledon.com ir.eledon.com/news-releases/news-release-details/eledon-presents-updated-data-ongoing-phase-1b-trial-evaluating-0

Eledon Presents Updated Data from Ongoing Phase 1b ... Data from patients who remained on tegoprubart for a year showed overall mean 12-month eGFR of approximately 68 mL/min/1.73 m² post- ...

5. journals.lww.com journals.lww.com/transplantjournal/fulltext/2025/06001/04_3__tegoprubart_as_cd40l_co_stimulation_blockade.27.aspx

tegoprubart as cd40l co-stimulation blockade in a non-toxic ... Compared to historical controls receiving tacrolimus-based immunosuppression, patients treated with tegoprubart experienced a greater reduction in insulin ...

6. science.org science.org/doi/10.1126/scitranslmed.adf6376

The anti-CD40L monoclonal antibody AT-1501 promotes ... These data support AT-1501 as a safe and effective agent to ... type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 39 ...