Tegoprubart for Kidney Transplant Rejection

Recruiting at 56 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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will evaluate the safety and efficacy of AT-1501 compared with tacrolimus in patients undergoing kidney transplantation.

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.

What safety data is available for Tegoprubart in kidney transplant rejection?

The provided research primarily discusses the safety and efficacy of tacrolimus (also known as FK506, Prograf, Advagraf, Astagraf XL) in kidney transplantation. Tacrolimus is a calcineurin inhibitor used in immunosuppressive regimens. Safety data from these studies indicate that tacrolimus is effective but associated with side effects such as hypertension, hyperglycemia, hypercholesterolemia, and infections, including CMV. The studies also compare different formulations of tacrolimus, showing similar patient and graft survival rates, with some variations in acute rejection and new-onset diabetes mellitus. However, none of the studies specifically address Tegoprubart (also known as AT-1501 or Anti-CD40 ligand monoclonal antibody) for kidney transplant rejection, so additional research would be needed to find specific safety data for Tegoprubart. ^{1 2 3 4 5}

Is the drug AT-1501 (Tegoprubart) a promising treatment for preventing kidney transplant rejection?

Yes, AT-1501 (Tegoprubart) is a promising drug for preventing kidney transplant rejection. It has shown success in nonhuman primates by helping transplanted kidneys survive longer and function better. This drug works by blocking a specific pathway that can lead to rejection, and it has been engineered to reduce certain risks seen in earlier treatments. These positive results suggest it could be effective in humans too. ^{6 7 8 9 10}

What data supports the idea that Tegoprubart for Kidney Transplant Rejection is an effective treatment?

The available research shows that Tegoprubart, also known as AT-1501, is effective in preventing kidney transplant rejection in nonhuman primates. In studies, Tegoprubart led to long-term survival of transplanted kidneys, indicating its potential as a treatment. Compared to conventional treatments, Tegoprubart resulted in better outcomes, such as higher levels of certain proteins that indicate kidney function and fewer complications like viral reactivation. This suggests that Tegoprubart could be a safer and more effective option for kidney transplant patients. ^{6 7 9 10 11}

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

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]

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]

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]

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]

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]

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]

Citations

1. 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]

2. 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]

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

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

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

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

5. China pubmed.ncbi.nlm.nih.gov

[Effect of CD40 blockade on acute renal graft rejection in rats]. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Single-center experience with tacrolimus-based immunosuppressive regimens in renal transplantation. [2019]

7. United States 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. [2022]

8. United States 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients. [2021]

10. United States 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. [2015]

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

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