TCD601 for Kidney Transplant Rejection Prevention

Not currently recruiting at 5 trial locations

Overseen By Shannon Zentmeyer, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ITB-Med LLC

Disqualifiers: Cancer, Anti-HLA DSA, 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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called TCD601 (also known as Siplizumab or MEDI-507) to help prevent kidney transplant rejection. The goal is to determine the best way to use TCD601 with other treatments to help the body accept a new kidney from a living donor. The trial includes two groups, both receiving TCD601 with standard care, to identify the most effective approach. It seeks participants receiving their first kidney transplant from a living donor who is not a perfect match but is compatible in blood type. 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 TCD601 is likely to be safe for humans?

Research has shown that TCD601, also known as siplizumab, has been tested in people and is generally safe, meaning most patients tolerate it well. Studies have found that most side effects are mild and temporary, so any discomfort from the treatment usually doesn't last long or cause serious problems. As TCD601 is still undergoing a phase 2 trial, researchers are carefully studying its safety to ensure it is safe for more people in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for preventing kidney transplant rejection, which typically includes drugs like tacrolimus and mycophenolate mofetil, TCD601 offers a new approach. Researchers are excited because TCD601 is administered alongside non-myeloablative conditioning, potentially reducing the need for high-dose immunosuppressants, which can have significant side effects. This treatment aims to better balance the immune system, reducing rejection risk while minimizing harm to the patient.

What evidence suggests that TCD601 might be an effective treatment for kidney transplant rejection prevention?

Research has shown that TCD601, which contains siplizumab, may help prevent kidney transplant rejection. Siplizumab lowers the activity of natural killer (NK) cells, which play a role in rejecting transplants. After the first dose, the treatment reduced NK cell activity, but this effect diminished by day 33. Although this suggests a temporary effect, siplizumab is used alongside other methods to help the body accept the new kidney. Early results are promising, but further research is needed to confirm its long-term effectiveness. Participants in this trial will receive TCD601 with non-myeloablative conditioning and standard immunosuppression. ^{1 2 3 6 7}

Who Is on the Research Team?

Tracy Killingsworth

Principal Investigator

Nefro Avillion

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 who are receiving their first or second kidney transplant from a living donor who's at least a half-match. Participants must understand the study and agree to its terms. People with cancer, specific donor antibodies, or women able to have children cannot join.

Inclusion Criteria

Able to understand the study requirements and provide written informed consent before and study assessment is performed

I have received a kidney transplant from a partially matched living donor.

Exclusion Criteria

I have had cancer before.

I am a woman who could become pregnant.

Donor-specific Antibody

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TCD601 with non-myeloablative conditioning and standard of care immunosuppression

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• TCD601

Trial Overview The PANORAMA study is testing TCD601 (siplizumab) combined with bone marrow cells from the donor and a special conditioning treatment in new kidney transplant patients to see if it helps them accept the organ without long-term immune suppression.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 1 Intervention

TCD601administered with non-myeloablative conditioning and standard of care immunosuppression

Group II: Arm 1 Experimental Treatment 1 Intervention

TCD601administered with non-myeloablative conditioning and standard of care immunosuppression

Who Is Running the Clinical Trial?

ITB-Med LLC

Lead Sponsor

Trials

12

Recruited

390+

Published Research Related to This Trial

In a trial involving 80 kidney transplant recipients with preformed donor-specific antibodies, eculizumab significantly reduced the treatment failure rate to 8.8%, compared to an expected 40% with standard care, indicating its efficacy in preventing acute antibody-mediated rejection (AMR).

Eculizumab was well tolerated with no new safety concerns, and at 36 months, the graft and patient survival rates were 83.4% and 91.5%, respectively, suggesting it is a safe option for prophylaxis against AMR in kidney transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies. Glotz, D., Russ, G., Rostaing, L., et al.[2023]

In a study of 380 kidney transplant recipients, basiliximab significantly reduced the incidence of acute rejection episodes by 32% compared to placebo, demonstrating its efficacy in preventing rejection after transplantation.

Basiliximab was well-tolerated with no significant safety concerns, and it did not increase the risk of infections or other adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group. Nashan, B., Moore, R., Amlot, P., et al.[2022]

In a clinical trial involving 30 kidney transplant recipients, tocilizumab treatment significantly increased regulatory T cells (Tregs) and improved graft inflammation scores compared to controls, suggesting it effectively modulates the immune response post-transplant.

The treatment was well tolerated, with no reported patient deaths or graft losses, indicating a favorable safety profile for using IL-6 blockade in managing transplant-related immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial. Chandran, S., Leung, J., Hu, C., et al.[2023]

Siplizumab, an anti-CD2 monoclonal antibody, showed an acceptable safety profile in a phase 1 study with 13 renal allograft recipients, where mild infusion reactions were the most common adverse events.

The drug effectively reduced natural killer (NK) cell cytotoxicity after the first dose, but levels returned to above pretreatment values by day 33, indicating a potential mechanism for preventing renal allograft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile, pharmacokinetics, and pharmacodynamics of siplizumab, a humanized anti-CD2 monoclonal antibody, in renal allograft recipients. Pruett, TL., McGory, RW., Wright, FH., et al.[2019]

Tocilizumab (TCZ), an anti-IL-6R monoclonal antibody, shows promise as a treatment for antibody-mediated rejection (ABMR) in kidney transplant patients, with studies indicating significant reductions in donor-specific antibodies and inflammation, as well as stabilization of renal function in 117 patients reviewed.

The safety profile of TCZ appears favorable, with light to moderate adverse events and no increase in infection rates compared to standard-of-care treatments, suggesting it could be a viable alternative for managing ABMR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review. Cabezas, L., Jouve, T., Malvezzi, P., et al.[2022]

Siplizumab, a humanized monoclonal antibody, demonstrated a longer half-life and fewer adverse events compared to its rat counterpart BTI-322 in a study involving 14 chimpanzees, indicating a potentially safer profile for clinical use.

Both antibodies caused a rapid depletion of CD2+ lymphocytes, but immune recovery was faster with BTI-322, suggesting differences in their pharmacodynamics that could impact their use in transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody. Sellberg, F., Berglund, D., Binder, C., et al.[2020]

In a study of 40 kidney transplant recipients treated with tocilizumab (TCZ) for chronic antibody-mediated rejection (cABMR), the drug helped prevent clinical and histological worsening of the condition, although it was less effective in patients with more severe illness.

After 12 months, there was no significant change in renal function (eGFR) for most patients, and while some histological scores improved, the chronic glomerulopathy score increased, indicating the need for further research to assess the overall benefits and risks of TCZ in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring. Noble, J., Giovannini, D., Laamech, R., et al.[2022]

In a phase 2 study involving 102 sensitized kidney transplant recipients, eculizumab was found to be well tolerated with no new safety concerns, showing a treatment failure rate of 9.8% compared to 13.7% for standard of care, although this difference was not statistically significant.

When including grade I acute antibody-mediated rejection (AMR) in the analysis, eculizumab demonstrated a potential benefit with a treatment failure rate of 11.8% versus 29.4% for standard care, suggesting it may be more effective in preventing AMR in sensitized patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial. Marks, WH., Mamode, N., Montgomery, RA., et al.[2023]

Recent immunosuppressive drugs like mycophenolate mofetil and basiliximab, along with calcineurin inhibitors, have significantly decreased the rates of acute rejection in kidney transplants.

Newly developed agents such as CTLA4-Ig, LEA29Y, rituximab, and FTY720 are being introduced, and there are evolving protocols that allow for the withdrawal of steroids or calcineurin inhibitors, enhancing the safety and efficacy of kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Renal transplantation]. Hattori, R., Ono, Y., Oshima, S.[2014]

Monoclonal antibodies, such as basiliximab and daclizumab, are effective in reducing acute rejection in renal transplantation without significant side effects, but they have not yet shown improvements in long-term graft or patient survival.

Rituximab and eculizumab are used for specific cases like antibody-mediated rejection and post-transplant complications, highlighting the potential of monoclonal antibodies in enhancing transplant outcomes, although safety concerns have slowed the development of new therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of monoclonal antibodies in renal transplantation. van den Hoogen, MW., Hilbrands, LB.[2021]

Citations

1. withpower.com withpower.com/trial/phase-3-6-2021-d40e2

TCD601 for Kidney Transplant Rejection Prevention The drug effectively reduced natural killer (NK) cell cytotoxicity after the first dose, but levels returned to above pretreatment values by day 33, indicating ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04803058

A Study of TCD601 in the Induction of Tolerance in Renal ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

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

Safety Profile, Pharmacokinetics, and Pharmacodynamics ... We report the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of siplizumab, a humanized IgG1 anti-CD2 monoclonal antibody and potential ...

4. clinicaltrials.eu clinicaltrials.eu/inn/siplizumab/

Siplizumab – Application in Therapy and Current Clinical ... Study on Siplizumab and Rabbit Anti-Thymocyte Globulin for Preventing Rejection in New Kidney Transplant Patients. This clinical trial is focused on patients ...

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

Clinical Protocol TCD601B102 Siplizumab pharmacokinetics in renal transplant patients can be described by a 1-compartment model with 2 parallel mechanisms of clearance ...

6. journals.lww.com journals.lww.com/transplantjournal/fulltext/1998/10270/pharmacokinetics_and_safety_of_medi_507,_a.248.aspx

PHARMACOKINETICS AND SAFETY OF MEDI-507, A ... MEDI-507 (M507) is a humanized IgG1 anti-CD2 monoclonal antibody (mAb) derived from BTI-322, a rat mAb which has activity in preventing acute renal allograft ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7017722/

Safety and pharmacodynamics of anti-CD2 monoclonal ... We report the safety profile and efficacy of two modifications of the same anti-CD2 monoclonal antibody in cynomolgus macaques.