A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Zampilimab in Adult Kidney Transplant Recipients With Chronic Allograft Injury

Study Overview
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Brief Summary
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The main purpose of the study is to investigate the safety and tolerability of repeat dosing with zampilimab in kidney transplant recipients with deteriorating kidney function associated with chronic allograft injury (CAI).

Official Title
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A Multicenter, Randomized, Placebo-Controlled Investigator-Blind, Participant-Blind Study to Evaluate Safety/Tolerability, Pharmacokinetics, and Pharmacodynamics of Zampilimab in Adult Kidney Transplant Recipients With Chronic Allograft Injury

Conditions
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Chronic Allograft Injury

Intervention / Treatment
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* Drug: Zampilimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Functioning living or deceased donor allograft >=1 year post-transplantation Baseline (screening) biopsy showing Grade II or III interstitial fibrosis/tubular atrophy (IF/TA) (>=25% IF/TA) Progressive loss in kidney function observed after the first year post-transplant, defined as an estimated glomerular filtration rate (eGFR) decline of ≥3 mL/min/year for at least 24 months prior to screening, with a minimum of 2 documented measurements per year (minimum of 4 documented measurements in the 24-month period, performed at least 1 month apart) An eGFR >=30 mL/min/1.73 m^2 for a period of 6 months up to screening Stable standard of care concomitant medication for 3 months prior to screening Participant is male or female, >=18 years of age Exclusion Criteria: Recipient of multi-organ transplant (with the exception of repeated kidney transplant recipients, and/or corneal transplant recipients) Screening biopsy shows evidence of significant active antibody-mediated rejection that may affect the conduct of the study (eg, require change in treatment) according to the Principal Investigator (PI) Screening biopsy shows evidence of T cell-mediated rejection that may affect the conduct of the study (eg, require change in treatment) according to the PI Screening biopsy shows evidence of de novo or recurrent glomerular disease that may affect the conduct of the study (eg, require change in treatment) according to the PI Proteinuria ≥1500 mg/g at screening Participant who has a history of biopsy-proven acute rejection or treatment for suspected acute rejection within 3 months prior to screening Participant has had major surgery (including joint surgery) within 6 months prior to screening, or has planned surgery within 6 months after the last dose of investigational medicinal product (IMP) Participant has a current diagnosis of foot ulcer or diagnosis of chronic diabetic ulcer or history of delayed wound healing Participant has taken concomitant medication of sirolimus or everolimus within 3 months of screening

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zampilimab Cohorts<br>Participants will be randomized to receive zampilimab (UCB7858). | Drug: Zampilimab<br>* Participants will receive zampilimab (UCB7858) at pre-specified time-points.<br>* Other names: UCB7858;|
| Placebo Comparator: Placebo<br>Participants randomized to this arm will receive matching Placebo. | Drug: Placebo<br>* Participants will receive matching placebo (PBO) at pre-specified time-points.<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) | A treatment-emergent adverse event (TEAE) is defined as any event not present prior to the administration of investigational medicinal product (IMP) or any unresolved event already present before administration of IMP that worsens in intensity following exposure to the treatment. | From Day 1 (Baseline) to the end of Safety Follow-up Visit (up to Day 680) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of zampilimab | Serum concentration of the drug zampilimab from Baseline to the end of the last Safety Follow-up Visit | From Day 1 (Baseline) to the end of Safety Follow-up Visit (up to Day 680) | 
| Urine concentration of zampilimab | Urine concentration of the drug zampilimab from Baseline to the end of the last Safety Follow-up Visit | From Day 1 (Baseline) to the end of Safety Follow-up Visit (up to Day 680) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAI, Chronic Allograft Injury, UCB7858, Kidney transplantation, zampilimab