TCD601 + Belatacept for Kidney Transplant

(ASCEND Trial)

Not currently recruiting at 28 trial locations

Overseen By Britain Javens, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ITB-Med LLC

Disqualifiers: Previous kidney transplant, HLA identical donor, cardiac death donor

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: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals who have just received a kidney transplant. The researchers aim to determine if using TCD601 (also known as Siplizumab, an experimental treatment) with Belatacept offers a safer and more effective option compared to standard immunosuppression medicines. Participants will be divided into groups to compare different treatment combinations. This trial may suit someone receiving their first kidney transplant from a non-identical donor and who has not previously undergone a kidney transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that the combination of TCD601 (siplizumab) and Belatacept has been studied in kidney transplant patients. Early findings suggest that this combination is generally safe, and previous studies found that patients tolerated the treatment well.

Belatacept has undergone extensive study and is known to carry some risks, such as infections or certain types of cancer, but these are closely monitored in clinical settings. While detailed studies on TCD601 are not yet available, early research indicates it was generally safe in initial trials.

Overall, earlier research suggests that the combination of TCD601 and Belatacept holds promise in terms of safety. However, discussing potential risks and benefits with a doctor is crucial before joining any clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about TCD601 for kidney transplants because it introduces a new mechanism of action by targeting CD2, which could offer better immune system modulation. Unlike traditional treatments that often rely heavily on medications like tacrolimus (TAC) and antithymocyte globulin (ATG), TCD601 is combined with belatacept, which itself blocks a different pathway, potentially reducing the side effects linked to standard immunosuppressive therapies. This approach could lead to improved organ acceptance with fewer complications, making it a promising alternative to existing options.

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

In this trial, one group of participants will receive TCD601 (siplizumab) combined with Belatacept, mycophenolic acid (MPA), and corticosteroids. Research has shown that TCD601 with Belatacept can significantly reduce T cell activity, which is crucial because T cells play a role in rejecting a new kidney. Studies have found that Belatacept alone can improve kidney function in transplant patients without causing major drug interactions. Adding TCD601 to Belatacept may enhance its ability to prevent organ rejection. Although no controlled studies on TCD601 exist yet, early results suggest it could improve transplant success. ^{3 6 7 8 9}

Who Is on the Research Team?

Fredrik Juhlin

Principal Investigator

ITB-Med LLC

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 70 who are getting a new kidney from either a living donor or deceased with a matching blood type but not necessarily an exact tissue match. They must understand the study and agree to participate.

Inclusion Criteria

You understand what the study involves and can give written permission before any study tests are done.

You received a kidney transplant from a deceased or living donor who is a good match for you.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TCD601 in combination with belatacept, MPA, and corticosteroids or standard of care immunosuppression therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATG
• Belatacept
• Corticosteroids
• MPA
• TAC
• TCD601

Trial Overview The trial is testing TCD601 in combination with Belatacept against standard immunosuppression treatments in patients receiving their first kidney transplant, aiming to see if it's safe and works well.

How Is the Trial Designed?

Group I: TCD601 (siplizumab) Experimental Treatment 4 Interventions

TCD601 administered in combination with belatacept, mycophenolic Acid (MPA), and corticosteroids

Group II: ATG Active Control 4 Interventions

Antithymocyte globulin (ATG), tacrolimus (TAC), mycophenolic acid (MPA), and corticosteroids

ATG is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Approved in European Union as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Approved in Canada as Thymoglobulin for:

• Prevention and treatment of acute rejection in patients undergoing kidney transplantation
• Treatment of aplastic anemia in patients who are not candidates for bone marrow transplantation

Who Is Running the Clinical Trial?

ITB-Med LLC

Lead Sponsor

Trials

12

Recruited

390+

Published Research Related to This Trial

In a 12-month study involving 19 kidney transplant recipients, belatacept therapy combined with alemtuzumab induction showed similar kidney function and graft survival rates compared to tacrolimus, indicating its potential as a safe alternative for kidneys with preexisting pathology.

The rates of acute rejection at 12 months were comparable between belatacept (26%) and tacrolimus (16%) recipients, suggesting that belatacept may be as effective as traditional therapies in preventing rejection in these high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts. Sparkes, T., Ravichandran, B., Opara, O., et al.[2020]

A modified release tacrolimus formulation (MR4) is currently in phase III trials and aims to improve kidney transplant outcomes by allowing once-daily administration while maintaining the same therapeutic target levels as the original formulation.

Belatacept (LEA29Y), a second-generation immunosuppressant, has shown comparable efficacy to ciclosporin in phase II trials and is now in phase III trials, indicating its potential as a viable alternative for kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for De Novo renal transplantation: what's in the pipeline? Tedesco Silva, H., Pinheiro Machado, P., Rosso Felipe, C., et al.[2018]

Belatacept, a new immunosuppressant for kidney transplantation, has shown superior graft function and better preservation of renal structure compared to traditional treatments like cyclosporine, based on phase II and III clinical trials.

However, belatacept is associated with a higher risk of cellular rejection and post-transplant lymphoproliferative disorder (PTLD), particularly in patients who are EBV seronegative, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: from rational design to clinical application. Wekerle, T., Grinyó, JM.[2017]

Thymoglobulin (TMG) induction for steroid-free immunosuppression in 13 high-risk pediatric kidney transplant recipients showed a significant decrease in lymphocyte counts at 3 months compared to a DAC-based protocol, but counts returned to normal by 6 months, indicating a temporary effect.

While TMG was associated with a higher trend of subclinical cytomegalovirus and BK viremia, there were no acute rejection episodes and overall graft function remained excellent, suggesting TMG is a safe alternative for immunosuppression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation. Li, L., Chaudhuri, A., Chen, A., et al.[2022]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

Thymoglobulin was found to be effective in pancreas transplant patients, achieving a 74% initial reversal of rejection episodes, particularly in high-risk recipients, with a patient survival rate of 93% and a pancreas graft survival rate of 71% after a mean follow-up of 6 months.

However, over half of the treatment courses required dose adjustments due to side effects like leukopenia, and infections were common, occurring in 38% of patients within 30 days, highlighting the immunosuppressive risks associated with this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymoglobulin for induction or rejection therapy in pancreas allograft recipients: a single centre experience. Trofe, J., Stratta, RJ., Egidi, MF., et al.[2019]

In a study of pediatric kidney transplant recipients, Thymoglobulin induction therapy resulted in a significantly lower incidence of acute rejection (33%) compared to ATGAM (50%), indicating its efficacy in preventing rejection.

However, Thymoglobulin was associated with a higher rate of Epstein-Barr virus (EBV) infection (8% vs. 3% for ATGAM), suggesting the need for careful monitoring of EBV in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant recipients: a single-center report. Khositseth, S., Matas, A., Cook, ME., et al.[2019]

In a study of six patients with steroid-resistant T-cell-mediated rejection after kidney transplantation, anti-thymocyte globulin (ATG) treatment led to a significant increase in T-cell repopulation from 24% to 75%, primarily driven by effector memory CD8+ T cells.

The administration of ATG also resulted in an increase in regulatory T cells, suggesting a potential mechanism for modulating immune responses, while other immune cell types like B cells and natural killer cells showed no significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Immune Cell Repopulation After Anti-thymocyte Globulin Administration for Steroid-Resistant T-cell-mediated Rejection. Sim, JH., Han, SS., Lee, DS., et al.[2020]

In a case study of an HIV-positive kidney transplant recipient, early conversion to belatacept improved renal function without causing HIV disease progression or opportunistic infections.

The case suggests that belatacept can be a safe and effective option for enhancing kidney function while minimizing drug interactions, even after the use of anti-thymocyte globulin (ATG).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept conversion in an HIV-positive kidney transplant recipient following anti-thymocyte globulin induction. Kuten, SA., Patel, SJ., Baru, A., et al.[2018]

In a proof-of-concept study involving 12 kidney transplant recipients, a regimen combining belatacept, mycophenolic acid, steroids, and rabbit anti-thymocyte globulin significantly reduced acute rejection rates, with only 2 out of 12 patients experiencing rejection.

The study demonstrated that this treatment approach was safe, as no patients developed serious complications like post-transplant lymphoproliferative disorder, and all patients maintained their grafts without any deaths during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: a proof-of-concept study. Cicora, F., Mos, F., Petroni, J., et al.[2015]

In a 1-year study involving 89 kidney transplant recipients, belatacept-based regimens allowed over two-thirds of patients to avoid both calcineurin inhibitors and corticosteroids, which are known to have toxic effects.

Patients receiving belatacept had better renal function, with glomerular filtration rates 8-10 mL/min higher than those on a tacrolimus-based regimen, while maintaining comparable safety and low rates of acute rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppression with belatacept-based, corticosteroid-avoiding regimens in de novo kidney transplant recipients. Ferguson, R., Grinyó, J., Vincenti, F., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05669001

NCT05669001 | A Study of TCD601 in de Novo Renal ... The purpose of this study is to evaluate the safety and efficacy of TCD601 in combination with Belatacept when compared to standard of care immunosuppression ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05669001

A Study of TCD601 in de Novo Renal Transplant Recipients The purpose of this study is to evaluate the safety and efficacy of TCD601 in combination with Belatacept when compared to standard of care immunosuppression ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/32/NCT04311632/Prot_000.pdf

Clinical Protocol TCD601B102 In the completed renal transplant siplizumab clinical trials, no controlled studies have been performed, therefore the comparative safety ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1600613523005208

Siplizumab combination therapy with belatacept or ... The combination of siplizumab with belatacept or abatacept induced near-complete suppression of T cell proliferation and increased the potency of siplizumab- ...

5. withpower.com withpower.com/trial/phase-2-kidney-transplantation-3-2023-d51fd

TCD601 + Belatacept for Kidney Transplant (ASCEND Trial) Belatacept has been shown to improve kidney function in transplant recipients and avoid significant drug interactions, even after anti-thymocyte globulin (ATG) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05669001

NCT05669001 | A Study of TCD601 in de Novo Renal ... The purpose of this study is to evaluate the safety and efficacy of TCD601 in combination with Belatacept when compared to standard of care immunosuppression ...

7. nulojixhcp.bmscustomerconnect.com nulojixhcp.bmscustomerconnect.com/pooled-safety.html

Selected Pooled Safety Data See NULOJIX® (belatacept) pooled safety results: Boxed WARNINGS, PTLD, malignancies, PML, infections, adverse reactions, blood pressure, lipids, NODAT; ...

8. loyolamedicine.org loyolamedicine.org/clinical-research/clinical-trials/NCT05669001

NCT05669001 The purpose of this study is to evaluate the safety and efficacy of TCD601 in combination with Belatacept when compared to standard of care immunosuppression ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0041134509014225

Safety Profile, Pharmacokinetics, and Pharmacodynamics ... 127 Siplizumab combination therapy with belatacept or abatacept broadly ... safe in initial phase 1 dosing studies in renal transplant recipients.129 ...