AT-1501 for Kidney Transplant

Recruiting at 9 trial locations

Overseen By Eledon Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eledon Pharmaceuticals

Must not be taking: Immunosuppressants, Biologics, Steroids

Disqualifiers: Previous transplants, Anticoagulation, others

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

Compensation: Varies

Number of Visits: 13

Duration: 12 months

48 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 (also known as Tegoprubart or Anti-CD40 ligand monoclonal antibody) for individuals receiving their first kidney transplant. The aim is to determine if AT-1501 is safe and effective for these patients. Administered as an IV infusion, AT-1501 targets a specific protein involved in the immune response. Those about to undergo their first kidney transplant, without prior organ transplants or certain other conditions, might be suitable for this trial.

As a Phase 1, Phase 2 trial, this research seeks to understand how AT-1501 works in people and measures its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in kidney transplant treatment.

Do I have to stop taking my current medications for the trial?

The trial requires that you are not currently treated with any systemic immunosuppressive regimen, except for 5 mg prednisone or equivalent daily. If you are on other immunosuppressive medications, you may need to stop them to participate.

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

Research has shown that AT-1501, a type of antibody, appears safe in early studies. For instance, tests on animals such as monkeys found that AT-1501 helped kidney transplants function effectively without causing serious issues like blood clots.

Other studies on a similar antibody, tegoprubart, have also shown it to be safe and well-tolerated in people. These findings suggest that AT-1501 is likely safe. However, since this study remains in the early stages, there may be risks that have not yet been identified. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AT-1501 is unique because it targets CD40L, a protein involved in immune responses, using a monoclonal antibody. This approach is different from current treatments like calcineurin inhibitors, which suppress the immune system more broadly. By specifically targeting CD40L, AT-1501 aims to reduce the risk of organ rejection with potentially fewer side effects. Researchers are excited about this treatment because it could offer a more precise and possibly safer way to support kidney transplant success.

What evidence suggests that AT-1501 might be an effective treatment for kidney transplantation?

Research has shown that AT-1501, a type of antibody, could benefit kidney transplants. In animal studies, AT-1501 helped kidney transplants last longer and function better. Importantly, this treatment did not cause blood clots, a common issue with similar treatments. Another study suggested that AT-1501 might improve kidney transplant outcomes over time. These findings support AT-1501 as a potential new treatment to help prevent rejection in kidney transplant patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Jeff Bornstein, MD

Principal Investigator

Eledon Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 receiving their first kidney transplant from a living or deceased donor. It's not for those who've had previous transplants, are on current immunosuppressives (except low-dose prednisone), have used AT-1501 or similar drugs before, or will get kidneys with long cold times (>30 hours) or from donors meeting certain criteria like age and health conditions.

Inclusion Criteria

Agree to comply with contraception requirements during and for at least 90 days after the last administration of study drug

I have received my first kidney transplant.

Exclusion Criteria

My kidney donor matches one of the specific criteria needed.

I have never been treated with AT 1501 or any anti CD40LG therapy.

I am not on strong immune system suppressing drugs, except for a low dose of prednisone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive AT-1501 in combination with rATG induction, corticosteroids, and mycophenolate as maintenance therapy

12 months

Multiple visits (in-person) on Days 0, 7, 14, 21 and Months 1, 3, 6, 9, 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

Visits at Months 12 and 15

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AT-1501

Trial Overview The study tests the safety, how the body processes (pharmacokinetics), and effectiveness of a drug called AT-1501 in patients getting a kidney transplant. Participants will receive this medication to see if it helps prevent organ rejection without causing significant harm.

How Is the Trial Designed?

Group I: AT-1501 Single Arm Experimental Treatment 1 Intervention

AT-1501 monoclonal antibody targeting CD40L given as an IV infusion

Who Is Running the Clinical Trial?

Eledon Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

300+

Published Research Related to This Trial

The novel fully human anti-CD40 monoclonal antibody 4D11 significantly prolonged kidney graft survival in cynomolgus monkeys, with survival times ranging from 84 to 379 days depending on the dosage, compared to only 5-7 days in the control group.

4D11 demonstrated a favorable safety profile, as only one animal developed an anti-4D11 antibody, suggesting it may be a promising alternative for preventing organ rejection without the thromboembolic complications associated with anti-CD154 monoclonal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys. Imai, A., Suzuki, T., Sugitani, A., et al.[2021]

The novel anti-CD40 monoclonal antibody ASKP1240 significantly prolonged renal allograft survival in Cynomolgus monkeys, demonstrating its efficacy as a potential treatment for preventing organ rejection.

ASKP1240 was effective both as a monotherapy and in combination with low doses of other immunosuppressive drugs, without causing significant side effects or inducing cytokine release, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ASKP1240 combined with tacrolimus or mycophenolate mofetil on renal allograft survival in Cynomolgus monkeys. Song, L., Ma, A., Dun, H., et al.[2021]

Both anti CD40 and anti CD40L (CD154) treatments effectively prevented acute and long-term kidney transplant rejection in nonhuman primates, with a significant increase in rejection-free survival compared to untreated animals (6 days).

Anti CD154 treatment showed a longer median rejection-free survival (352 days) compared to anti CD40 treatment (131 days), indicating that CD154 inhibition may provide a more durable solution for preventing transplant rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Inhibition of CD40/CD154 Costimulatory Signaling in the Prevention of Renal Transplant Rejection in Nonhuman Primates: A Systematic Review and Meta Analysis. Perrin, S., Magill, M.[2022]

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 using severe combined immunodeficient (SCID) mice, blockade of CD40-CD154 interactions significantly reduced kidney damage caused by adriamycin nephropathy, showing less histological injury and improved kidney function compared to control mice.

The protective effect of CD40-CD154 blockade appears to be linked to reduced macrophage infiltration and decreased expression of pro-inflammatory markers, suggesting that this intervention may inhibit harmful immune responses in kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis. Lee, VW., Qin, X., Wang, Y., et al.[2017]

The anti-CD154 monoclonal antibody TNX-1500 effectively prevents kidney allograft rejection without causing platelet activation or thromboembolic complications, as shown in both in vitro and in vivo studies.

Unlike previous immunoglobulin G1 antibodies, TNX-1500 was engineered to minimize binding to Fc-gamma receptor IIa, which is responsible for the thrombogenic effects, while maintaining its efficacy in preventing organ rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TNX-1500, a crystallizable fragment-modified anti-CD154 antibody, prolongs nonhuman primate renal allograft survival. Lassiter, G., Otsuka, R., Hirose, T., et al.[2023]

The novel anti-human CD154 domain antibody (dAb, BMS-986004) effectively blocks CD40-CD154 interactions, significantly prolonging kidney transplant survival in a nonhuman primate model without causing thromboembolism, achieving a median survival time of 103 days.

When combined with conventional immunosuppression, the anti-CD154 dAb further enhanced allograft survival, resulting in a median survival time of 397 days, and increased the frequency of regulatory T cells, indicating a potential for improved graft acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection. Kim, SC., Wakwe, W., Higginbotham, LB., et al.[2023]

The administration of a CD154-specific monoclonal antibody (hu5C8) in rhesus monkeys allowed successful kidney transplants without acute rejection, with effects lasting over 10 months after treatment ended.

This therapy does not require the depletion of T or B cells and shows promise for human transplantation, as treated monkeys remained healthy and maintained some immune response without harming the transplanted organ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Kirk, AD., Burkly, LC., Batty, DS., et al.[2022]

Citations

1. 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.

2. 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- ...

3. journals.lww.com journals.lww.com/jasn/fulltext/2023/11001/tegoprubart_for_the_prevention_of_rejection_in.1140.aspx

Tegoprubart for the Prevention of Rejection in Kidney... Improved graft function may improve long term outcomes in kidney transplantation. It is postulated that tegoprubart could be an alternative therapy for ...

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

The anti-CD40L monoclonal antibody AT-1501 promotes ... AT-1501 promoted survival and function of islet and kidney allografts in cynomolgus and rhesus macaques, respectively, without evidence of thromboembolism.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10287837/

CD40-CD40L Blockade: Update on Novel Investigational ... In this review, we discuss newer agents undergoing clinical trials to interrupt CD40/CD40L interactions in transplantation to prolong graft survival.

6. ir.eledon.com ir.eledon.com/news-releases/news-release-details/eledon-pharmaceuticals-announces-use-tegoprubart-key-component

Eledon Pharmaceuticals Announces Use of Tegoprubart ... Our anti-CD40L antibody tegoprubart represents a novel approach to immunosuppression therapy with the potential to improve safety and efficacy ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11527214/

Safety and tolerability of tegoprubart in patients with ... This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals ...

8. scholars.duke.edu scholars.duke.edu/publication/1594864

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 nonhuman ...