A Study Comparing Siplizumab With Rabbit Anti-Thymocyte Globulin to Help the Body Accept a Kidney Transplant (MODERNIZE1)

Phase 2b, Randomized, Multicenter, Double-Blind, Dose-Finding, Active-Controlled Study of Siplizumab (TCD601) Compared to Rabbit Anti-Thymocyte Globulin in Renal Transplant Recipients Requiring Induction Therapy and Receiving Standard of Care Immunosuppression With Tacrolimus, Mycophenolic Acid and Corticosteroids

The goal of this clinical trial is to learn if siplizumab can prevent rejection of a kidney transplant in adult participants with end stage kidney disease. The main questions it aims to answer are:

How many adverse events do participants receiving two different doses of siplizumab have compared to rabbit anti-thymocyte globulin (rATG)?

How many participants successfully keep their kidney transplant after receiving siplizumab or rATG? This will be calculated as those participants that did not: die; have their kidney fail to work properly (graft loss); their body rejects their transplant (tissue sample (biopsy)-proven acute rejection: BPAR); or who were lost to follow-up.

How does the body respond to siplizumab after dosing at each of the 2 dose levels?

How does siplizumab work in the body compared to rATG?

Selected participants will be divided into 3 groups. In 2 of the groups, participants will be given siplizumab at one of the two study medicine doses. Participants in the third group will be given rATG. All participants will take the usual anti-rejection medicines given before, during, and after a kidney transplant. All participants will also be given medicines before the study drug to lower the risk of reactions, and medicines used to prevent or treat infections after the transplant.

Participants will be asked to provide their medical history at the first visit at the study site where you will have your kidney transplant. At the first visit and other visits participants will be asked to provide their medication history, have a physical exam, check vital signs, have blood drawn for tests, and have non-invasive tests that record the electrical activity of your heart (ECG) and blood draws.

Participants will be monitored for 12 months after transplant surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Transplant Failure and Rejection
• Intervention / Treatment: Drug: Siplizumab; Drug: Rabbit anti-thymocyte globulin

Detailed Description

Approximately 120 renal transplant candidates requiring induction therapy will be enrolled 1:1:1 to receive 1 of 2 dose levels of siplizumab or to the comparator rATG.

Randomization will be stratified by donor status (living vs donation after brain death vs donation after cardiac death) to ensure similar proportions of donor types in each study arm. All participants will also receive:

• A triple regimen (TAC, MPA, and CS) of background immunosuppressive therapy for the duration of the study.
• Premedication prior to study treatment infusions.
• Infection prophylaxis

This clinical trial will evaluate the safety of an anti-cluster of differentiation 2 (CD2) monoclonal antibody, siplizumab, compared to rATG as induction therapy in renal transplant recipients.

Following hospital discharge, participants will undergo assessments and procedures as indicated in the protocol through Month 12 or EOS, unless more frequent visits are required per local SoC or for laboratory specimen collection.

Safety assessments will include physical examinations, ECGs, vital signs, viral surveillance and monitoring, standard clinical laboratory evaluations completed centrally (hematology, clinical chemistry, urinalysis), and AE/SAE monitoring.

Final analysis will be performed when all participants have completed 12-month follow-up visits post-transplant or have otherwise ended the trial. This analysis will be performed to evaluate the safety of siplizumab at 2 dose levels compared to rATG.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Recipients of a renal allograft from a non-HLA identical living or deceased donor.
• Recipients of a kidney with a cold ischemia time < 30 hours; hypothermic machine perfusion within the same timeframe is acceptable.
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must agree to use highly effective methods of contraception.

Exclusion Criteria:

• Transplant recipients seronegative for EBV.
• Transplant recipients receiving a kidney from a non-heart beating donor (ie, DCD) whose organ is retrieved from an uncontrolled DCD or whose donor age > 55 years of age.
• Multi-organ transplant recipients (eg, kidney-pancreas, organ other than kidney), dual-kidney transplant recipients, recipients with more than one prior kidney transplant, or hematopoietic stem cell transplantation recipients.
• Presence of current or historical DSA via single-antigen bead assay or local SoC. The MFI cut-off value used to determine the presence of DSA will be defined as per the institutional SoC. Results within 3 months prior to transplant are acceptable.
• Crossmatch positive (isolated positive B cell crossmatches are not an exclusion criterion).
• ABO-incompatible recipient.
• Administration of complement inhibitor therapy within 6 months prior to the transplant, or likely to require treatment with complement inhibitor therapy during the study.
• Participants receiving immunosuppressive therapies prior to transplant for pre-existing conditions must be candidates for the protocol-defined regimen.
• History of malignancy of any organ system, except for localized excised non-melanomatous skin lesions or carcinoma in situ of the cervix.
• Seropositive for human immunodeficiency virus or hepatitis B surface antigen. Participants who are seropositive for hepatitis C virus (HCV) are excluded without proof of sustained viral response after anti-HCV treatment.
• Recipient of a kidney from a donor who tests positive for human immunodeficiency virus or hepatitis B surface antigen/hepatitis B core protein.
• History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (eg, siplizumab, rATG, TAC, MPA derivatives, CS).
• Evidence of active tuberculosis (TB) infection (participants with a history of latent TB may become eligible after treatment with anti-TB therapy according to national guidelines).
• Participants with severe systemic infection(s), at the time of screening or within 2 weeks prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose siplizumab	Drug: Siplizumab; A non-agonistic, humanized, anti-CD2 monoclonal antibody of the IgG1κ class; Other Names: TCD601
Experimental: High dose siplizumab	Drug: Siplizumab; A non-agonistic, humanized, anti-CD2 monoclonal antibody of the IgG1κ class; Other Names: TCD601
Active Comparator: Rabbit anti-thymocyte globulin	Drug: Rabbit anti-thymocyte globulin; An anti-human thymocyte immunoglobulin preparation made of purified polyclonal antibodies derived from rabbits; Other Names: Thymoglobulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the safety of 2 dose levels of siplizumab versus rATG.	Number and percentage of participants at 12 months post-transplant experiencing adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	Composite incidence of BPAR, death, graft loss, and loss-to-follow-up.; Incidence of participants who experienced BPAR as defined by central pathology (blinded independent central review using Banff Allograft Pathology Scoring).; Incidence of treated BPAR and steroid-resistant BPAR.	12 months
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	• Grade of BPAR.	12 months
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	• Severity of BPAR.	12 months
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	Time to first BPAR for each participant.; Time to graft loss for each participant.; Time to death for each participant.	12 months
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	Participant survival at 12 months.; Graft survival at 12 months.	12 months
Assessment of the incidence of composite efficacy failure (defined as death, graft loss, biopsy-proven acute rejection [BPAR], or loss-to-follow-up) and their individual components.	• Number of participants requiring for-cause renal allograft biopsy assessments over 12 months post-transplant.	12 months
Assessment of the pharmacokinetics (PK) of 2 dose levels of siplizumab.	Siplizumab Cmax (maximum blood concentration) over 12 weeks post-transplant.	12 weeks
Assessment of the pharmacokinetics (PK) of 2 dose levels of siplizumab.	Siplizumab AUC (area under the concentration-time curve) over 12 weeks post-transplant.	12 weeks
Assessment of the pharmacodynamics (PD) of 2 dose levels of siplizumab versus rATG.	Depletion and recovery of lymphocyte count by subset (total lymphocytes; CD3+, CD4+, and CD8+ T cells; CD19+ B cells; CD56+ NK cells) over 12 months post-transplant.	12 months

Collaborators and Investigators

• Sponsor: Nefro Avillion Clinical Development, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): April 29, 2026
• Primary Completion (Estimated): March 28, 2028
• Study Completion (Estimated): March 28, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Social Behavior; Rejection, Psychology; Amino Acids, Peptides, and Proteins; Proteins; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Immune Sera; Antilymphocyte Serum; thymoglobulin; siplizumab
• Other Study ID Numbers: TCD601B205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No