TCD601 for Kidney Transplant Rejection Prevention

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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a treatment that uses a special medicine, donor bone marrow cells, and mild pre-treatment to help patients receiving new kidney transplants from living donors accept their new organ.

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.

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

The drug siplizumab, which is part of TCD601, has been studied for its safety and potential to prevent kidney transplant rejection. Additionally, tocilizumab, a similar drug targeting inflammation, has shown promise in managing rejection in kidney transplant patients, suggesting that TCD601 may also be effective. ^{1 2 3 4 5}

Is TCD601 (Siplizumab) safe for human use?

Siplizumab, also known as TCD601, has been tested in humans and generally shows a good safety profile with only mild, temporary side effects reported. In studies, it caused a quick but temporary reduction in certain immune cells, and any side effects were mild and short-lived. ^{1 2 6 7 8}

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

TCD601, also known as siplizumab, is unique because it is a humanized anti-CD2 monoclonal antibody, which targets a specific protein on immune cells to prevent kidney transplant rejection. This mechanism is different from other treatments that often target different pathways or use a combination of therapies. ^{1 2 5 9 10}

Research Team

Nick Hryciw, MA

Principal Investigator

ITB-MED

Eligibility Criteria

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

I am between 18 and 60 years old.

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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 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 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]

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]

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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Japan pubmed.ncbi.nlm.nih.gov

[Renal transplantation]. [2014]

4. England 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. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

7. United States 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. [2023]

8. United States 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. [2023]

9. United States 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Use of monoclonal antibodies in renal transplantation. [2021]