A Dose Escalation Study in de Novo Renal Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of escalating doses of TCD601 when compared to rATG in de novo renal transplant patients.

Official Title
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A 12-Month, Randomized, Controlled, Open-Label, Dose Escalation Study Evaluating Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of an Anti-CD2 Monoclonal Antibody, TCD601(Siplizumab) Compared to Anti-thymocyte Globulin (rATG), as Induction Therapy in de Novo Renal Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Biological: TCD601
* Drug: Tacrolimus (TAC)
* Drug: Corticosteroids (CS)
* Drug: Mycophenolate Mofetil (MMF)
* Drug: ATG


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Able to understand the study requirements and provide written informed consent before and study assessment is performed. Male or female patients ≥ 18 to 70 years of age. Recipients of a de novo renal allograft from a heart-beating deceased, living unrelated, or non-HLA identical living related donor. Recipients of a kidney with a cold ischemia time (CIT) less than 30 hours. Key Exclusion Criteria: Multiple-organ transplant recipients Subjects who have received a kidney allograft previously Recipient of a kidney from an HLA identical living related donor Recipient of a kidney from a donor after cardiac death Subjects at high immunological risk for rejection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>TCD601 administered with the contemporary standard of care (SoC) consisting of concentration-controlled tacrolimus (TAC) combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Biological: TCD601<br>* Investigational Product<br>Drug: Tacrolimus (TAC)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Corticosteroids (CS)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Mycophenolate Mofetil (MMF)<br>* Standard of Care Concomitant Immunosuppression<br>|
| Experimental: Arm 2<br>TCD601 administered with the contemporary standard of care (SoC) consisting of concentration-controlled tacrolimus (TAC) combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Biological: TCD601<br>* Investigational Product<br>Drug: Tacrolimus (TAC)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Corticosteroids (CS)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Mycophenolate Mofetil (MMF)<br>* Standard of Care Concomitant Immunosuppression<br>|
| Experimental: Arm 3<br>TCD601 administered with the contemporary standard of care (SoC) consisting of concentration-controlled tacrolimus (TAC) combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Biological: TCD601<br>* Investigational Product<br>Drug: Tacrolimus (TAC)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Corticosteroids (CS)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Mycophenolate Mofetil (MMF)<br>* Standard of Care Concomitant Immunosuppression<br>|
| Experimental: Arm 4<br>TCD601 administered with the contemporary standard of care (SoC) consisting of concentration-controlled tacrolimus (TAC) combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Biological: TCD601<br>* Investigational Product<br>Drug: Tacrolimus (TAC)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Corticosteroids (CS)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Mycophenolate Mofetil (MMF)<br>* Standard of Care Concomitant Immunosuppression<br>|
| Active Comparator: Arm 5<br>ATG administered with the contemporary standard of care (SoC) consisting of concentration-controlled tacrolimus (TAC) combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Drug: Tacrolimus (TAC)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Corticosteroids (CS)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: Mycophenolate Mofetil (MMF)<br>* Standard of Care Concomitant Immunosuppression<br>Drug: ATG<br>* Standard of Care induction therapy in solid organ transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. |  | 12 months | 
| Measure Peak Plasma Concentration (Cmax) over time. | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration. | 12 months | 
| Measure the Area under the plasma concentration versus time curve (AUC). | The AUC from time zero to the last measurable concentration sampling time. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess changes in peripheral immunophenotype, including T-, B-, and NK-cells, via Fluorescence-activated Cell Sorter (FACS) over time. |  | 12 months | 
| Measure anti-TCD601 antibodies in serum via Enzyme-linked Immunosorbent (ELISA) assay over time. |  | 12 months | 
| Measure peripheral CD2-receptor occupancy following TCD601 administration | Receptor Occupancy will be reported as the % of target saturation. | 12 months |