Tegoprubart for Kidney Transplant Rejection

No longer recruiting at 58 trial locations

Overseen By Eledon Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eledon Pharmaceuticals

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Thromboembolic event, Hypercoagulable state, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

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, an anti-CD40 ligand monoclonal antibody) to determine its effectiveness in preventing kidney transplant rejection. Researchers aim to compare its efficacy against a standard drug, tacrolimus. The goal is to assess whether AT-1501 is safe and effective for kidney transplant recipients. This trial may suit individuals receiving their first kidney transplant from either a living or deceased donor. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

Yes, you must stop taking any systemic immunosuppressive medications and corticosteroids, except for topical or inhaled ones, to participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that AT-1501, also known as tegoprubart, appears safe. Studies in animals have found it safe and effective for kidney transplants. Current human results are encouraging, suggesting it could help prevent organ rejection in kidney transplant patients.

In contrast, tacrolimus, the other treatment in this study, is already widely used and approved by the FDA to prevent organ rejection. It is generally well-tolerated, though some patients may experience side effects like shaking or high blood pressure.

Overall, both treatments have demonstrated good safety in studies so far. AT-1501 is still undergoing testing, but the results are promising. Tacrolimus is a standard treatment with a known safety record. Participants should feel reassured by the existing data on both treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney transplant rejection?

Unlike the standard treatment for kidney transplant rejection, which typically involves immunosuppressants like Tacrolimus, AT-1501 is a monoclonal antibody that targets CD40L. This is a new mechanism of action that aims to modulate the immune response more precisely, potentially reducing the risk of rejection without the broad immunosuppression seen with current options. Researchers are excited about AT-1501 because it could offer a more targeted approach that minimizes side effects and improves long-term outcomes for transplant patients.

What evidence suggests that this trial's treatments could be effective for kidney transplant rejection?

In this trial, participants will receive either AT-1501, also known as tegoprubart, or Tacrolimus. Research has shown that AT-1501 can enhance the success of kidney transplants. In studies with animals similar to humans, AT-1501 improved the survival and function of transplanted kidneys without causing blood clots. Specifically, data from a year-long study found that patients taking tegoprubart maintained good kidney function, with an average filtration rate of about 68 mL/min/1.73 m². This suggests that tegoprubart could be a promising new option to prevent rejection after a kidney transplant. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults (18+) who are receiving their first kidney transplant from a living or deceased donor and agree to follow contraception rules post-treatment. It's not for those on chronic steroids/immunosuppressants, with clotting disorders, needing long-term anticoagulation, or previous severe reactions to similar drugs.

Inclusion Criteria

I have received my first kidney transplant.

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

Exclusion Criteria

I am planned to receive a specific initial immune system treatment other than rATG.

I am currently taking corticosteroids that are not just for skin or breathing.

My kidney transplant will involve a delay over 30 hours before implantation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AT-1501 or tacrolimus as part of the kidney transplantation procedure

6 months

Regular visits for IV infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Periodic visits for assessment

Long-term follow-up

Participants are monitored for long-term outcomes such as eGFR, NODAT, and graft survival

12 months

What Are the Treatments Tested in This Trial?

Interventions

• AT-1501
• Tacrolimus

Trial Overview The study compares the safety and effectiveness of a new drug called Tegoprubart (AT-1501) with Tacrolimus in preventing organ rejection after kidney transplantation. Participants will be randomly assigned to receive one of these treatments.

How Is the Trial Designed?

Group I: Investigative Experimental Treatment 1 Intervention

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

Group II: Comparator Active Control 1 Intervention

Tacrolimus administered BID, targeting a whole blood trough concentration of 6-12 ng/mL until Month 6, and 6-8 ng/mL thereafter

Who Is Running the Clinical Trial?

Eledon Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

300+

Published Research Related to This Trial

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]

In a study of 28 adult kidney transplant patients, tacrolimus demonstrated high efficacy with a 100% patient and graft survival rate at 6 months, although acute rejection occurred in 17.8% of patients, particularly in those who were highly sensitized.

While tacrolimus is effective, it is associated with notable side effects, including infections (35.7% of patients), hypertension (14%), and metabolic issues like hyperglycemia (32%), indicating the need for careful monitoring and longer-term studies to evaluate its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-center experience with tacrolimus-based immunosuppressive regimens in renal transplantation. Abou-Jaoude, MM., Almawi, WY.[2019]

A systematic review and network meta-analysis of 68 studies found that long-term outcomes, such as graft loss and patient mortality, are generally comparable between the once-daily tacrolimus formulation (Advagraf) and the twice-daily formulation (Prograf) in kidney transplant recipients.

The analysis showed that the rates of acute rejection and new-onset diabetes mellitus after transplantation varied by treatment, but both Advagraf and Prograf demonstrated similar effectiveness in preventing graft loss and mortality, indicating that either formulation can be a viable option for post-transplant care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. T A, M., Chng, R., Yau, WP.[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]

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]

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 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]

In a 5-year follow-up of the ADVANCE trial involving 1125 kidney transplant patients, overall graft survival rates were high at 88.1%, indicating that prolonged-release tacrolimus (PR-T) is effective for long-term immunosuppression.

Patient survival rates were also impressive at 94.4% after 5 years, with low rates of adverse drug reactions (1.5% likely related to tacrolimus), suggesting that PR-T is a safe option for kidney transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Prolonged-release Tacrolimus-based Immunosuppression in De Novo Kidney Transplant Recipients: 5-Y Prospective Follow-up of Patients in the ADVANCE Study. Pernin, V., Glyda, M., Viklický, O., et al.[2023]

The extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) shows similar efficacy to the immediate-release version (Prograf®) in kidney transplant recipients, with no significant differences in patient/graft survival, acute rejection rates, or renal function across studies involving over 2,500 patients.

Advagraf® significantly improves medication adherence compared to Prograf®, which is crucial for long-term transplant success, and it has also been associated with favorable outcomes when combined with mTOR inhibitors, potentially reducing the risk of late-onset cytomegalovirus infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. Noble, J., Jouve, T., Rostaing, L., et al.[2021]

Switching from the twice-daily tacrolimus (Prograf) to the once-daily extended-release formulation (Advagraf) in 49 kidney transplant patients led to an increased openness about their transplant experience after 6 months, indicating a potential improvement in quality of life.

However, 8 out of the 49 patients had to switch back to the original formulation due to adverse events, suggesting that while the switch may have benefits, it also carries risks that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of switching from twice-daily to once-daily tacrolimus formulation on quality of life, anxiety, and transplant benefit perception after kidney transplantation. Calia, R., Lai, C., Aceto, P., et al.[2015]

In a study involving Wistar rats as donors and male SD rats as recipients, the use of CD40L monoclonal antibody significantly reduced acute rejection of kidney transplants, with a mean rejection score of 0.63 in the therapy group compared to 3.72 in the control group.

The treatment was administered daily for four days following transplantation, demonstrating that CD40 blockade can effectively suppress acute renal graft rejection in this animal model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of CD40 blockade on acute renal graft rejection in rats]. Shi, XH., Liu, XY., Sun, XY., et al.[2017]

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. ir.eledon.com ir.eledon.com/news-releases/news-release-details/eledon-pharmaceuticals-present-results-phase-2-bestow-trial

Release Details Title: Efficacy and Safety of Tegoprubart for the Prevention of Rejection in Kidney Transplantation: Results from the Phase 2 BESTOW Trial

5. 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.

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 ... Currently, tegoprubart is being evaluated in three global clinical studies for the prevention of organ rejection in patients receiving kidney ...

7. amjtransplant.org amjtransplant.org/article/S1600-6135(25)00975-X/fulltext

Tegoprubart, an Anti-CD40L Antibody, for the Prevention of ... The most up to date safety, rejection, eGFR, and biomarker data will be presented. Conclusions: It is postulated that tegoprubart could be an alternative ...