TCD601 for Kidney Transplant Tolerance

(PERSPECTIVE Trial)

Recruiting at 7 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

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the drug TCD601 for kidney transplant tolerance?

The research on siplizumab, a component of TCD601, shows it has potential in preventing kidney transplant rejection by targeting specific immune cells. Additionally, similar treatments like Lulizumab have shown success in prolonging kidney graft survival in animal studies, suggesting that TCD601 might also help in improving transplant outcomes. ^{1 2 3 4 5}

Is TCD601 (Siplizumab) safe for human use?

Siplizumab, also known as TCD601, has been tested in humans and chimpanzees, showing few mild and temporary side effects in humans. It was generally well-tolerated, with fewer adverse effects compared to a similar antibody, BTI-322. ^{1 2 6 7 8}

How is the drug TCD601 different from other treatments for kidney transplant tolerance?

TCD601, also known as siplizumab, is unique because it is a humanized monoclonal antibody that targets CD2, a molecule on immune cells, to help prevent kidney transplant rejection. This mechanism is different from other treatments that often target different immune pathways or use a combination of therapies. ^{1 2 4 7 9}

What is the purpose of this trial?

This trial is testing TCD601 to help new kidney transplant patients from living donors accept their new organ without immune system rejection.

Research Team

Nick Hryciw, MA

Principal Investigator

ITB-MED

Eligibility Criteria

This trial is for adults aged 18 to 60 who are receiving their first or second kidney transplant from a living donor who's at least half-matched genetically and has the same blood type. Participants must understand the study and agree to its terms. Pregnant women, those able to have children, or individuals with a history of cancer 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

Donor-specific antibody

I am a woman who could become pregnant.

I have had cancer before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Treatment

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

6-8 weeks

Follow-up

Participants are monitored for safety, tolerability, and activity of the treatment regimen

24 months

Treatment Details

Interventions

• TCD601

Trial Overview The trial is testing TCD601 in patients getting new kidneys from living donors. It aims to see if this drug can help patients accept their new organ without the immune system attacking it (called 'tolerance').

Participant Groups

Group I: 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+

Findings from Research

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]

Desensitization using carfilzomib and lulizumab in a non-human primate model significantly reduced donor-specific antibodies and improved kidney graft survival, with a median survival time of 64.8 days compared to 5.8 days in control animals.

The treatment shifted the immune system towards a more naive phenotype, maintaining regulatory T cells and increasing naive CD4 T and B cells, although all desensitized subjects eventually developed antibody-mediated rejection (AMR) and graft failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model. Schroder, PM., Schmitz, R., Fitch, ZW., et al.[2022]

Achieving tolerance in kidney transplant recipients could significantly improve graft survival and reduce the toxic effects of long-term immunosuppression, with recent studies highlighting the roles of B and regulatory T cells in maintaining this tolerance.

Mixed hematopoietic chimerism has shown promise in inducing tolerance, allowing some patients to withdraw from immunosuppression, although this approach carries risks such as infections and graft versus host disease; combining this with regulatory cell therapies may enhance safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of tolerance in kidney transplantation. Chandran, S., Feng, S.[2018]

In a study of 10 sensitized kidney-transplant candidates treated with tocilizumab (TCZ) for desensitization, TCZ plasma concentrations showed high variability, ranging from less than 1.0 to 52.5 mg/L, with a median of 25.6 mg/L.

The study found no significant relationship between TCZ trough concentrations and the reduction of anti-HLA antibodies, suggesting that while TCZ is used for desensitization, its effectiveness may not directly correlate with its plasma levels, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization. Truffot, A., Jouve, T., Noble, J., et al.[2022]

Multidrug immunosuppressive protocols have significantly improved short-term survival rates for kidney transplant patients, increasing from 50% to 90%, but chronic graft rejection remains a major challenge leading to long-term failure.

Research suggests that enhancing the function and number of regulatory T cells could help induce specific tolerance to donor antigens, potentially reducing the need for lifelong immunosuppression and its associated severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific alloantigen self-control by regulatory T cells in organ transplantation: a review. Boschiero, L., Nacchia, F., Fior, F., et al.[2007]

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]

Eculizumab, an anti-C5 monoclonal antibody, has shown effectiveness in treating acute antibody-mediated rejection (AMR) in kidney transplant patients, but there are cases where it has failed, particularly in C4d-negative or C1q-negative AMR.

Two cases of AMR resistant to eculizumab were reported, indicating that these specific types of AMR may involve complement-independent mechanisms, suggesting a need for alternative treatments in such scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts. Burbach, M., Suberbielle, C., Brochériou, I., et al.[2022]

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]

References

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

Safety profile, pharmacokinetics, and pharmacodynamics of siplizumab, a humanized anti-CD2 monoclonal antibody, in renal allograft recipients. [2019]

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

Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Current status of tolerance in kidney transplantation. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab Trough Levels Variability in Kidney-Transplant Candidates Undergoing Desensitization. [2022]

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

Specific alloantigen self-control by regulatory T cells in organ transplantation: a review. [2007]

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

Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab in the Treatment of Chronic Antibody-Mediated Rejection Post Kidney Transplantation: Clinical and Histological Monitoring. [2022]

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

Report of the inefficacy of eculizumab in two cases of severe antibody-mediated rejection of renal grafts. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review. [2022]