AT-1501 for Kidney Transplant

Recruiting at 8 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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety, PK, and efficacy of AT 1501 in patients undergoing kidney transplantation.

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.

What data supports the idea that AT-1501 for Kidney Transplant is an effective drug?

The available research shows that AT-1501, when tested in nonhuman primates, led to long-term survival of kidney transplants. This suggests that it effectively prevents the body from rejecting the new kidney. Additionally, AT-1501 was found to be safer than previous treatments because it was designed to reduce the risk of blood clots. Compared to conventional treatments, AT-1501 also resulted in better overall health outcomes, such as higher levels of a protein that indicates good kidney function and fewer viral infections. This data supports the idea that AT-1501 is an effective and safer option for kidney transplant patients. ^{1 2 3 4 5}

What safety data exists for AT-1501 (Tegoprubart) in kidney transplants?

AT-1501, also known as Tegoprubart, is an anti-CD40 ligand monoclonal antibody designed to minimize thromboembolic complications. In nonhuman primate models, AT-1501 demonstrated long-term graft survival and function in both islet and kidney transplants without significant safety concerns. It showed reduced cytomegalovirus reactivation and no thromboembolic events, supporting its safety and efficacy for further clinical trials. ^{1 3 5 6 7}

Is the drug AT-1501 a promising treatment for kidney transplants?

Yes, AT-1501 is a promising drug for kidney transplants. It has shown to help kidney transplants last longer and work better in animal studies. It also seems to be safer than similar treatments used before. ^{1 2 3 6 8}

Research Team

Jeff Bornstein, MD

Principal Investigator

Eledon Pharmaceuticals

Eligibility Criteria

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

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of ASKP1240 combined with tacrolimus or mycophenolate mofetil on renal allograft survival in Cynomolgus monkeys. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys. [2021]

5. Switzerland 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

TNX-1500, a crystallizable fragment-modified anti-CD154 antibody, prolongs nonhuman primate renal allograft survival. [2023]