Safety, Pharmacokinetics, and Efficacy of AT 1501 in Patients Undergoing Kidney Transplant

Study Overview
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Brief Summary
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This study will evaluate the safety, PK, and efficacy of AT 1501 in patients undergoing kidney transplantation.

Detailed Description
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This study will evaluate the safety, PK, and efficacy of AT 1501 in patients undergoing kidney transplantation. Up to 24 de novo kidney transplant recipients will receive AT-1501 in combination with rATG induction with corticosteroids (CS), and mycophenolate as maintenance therapy.

Official Title
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A Phase 1b, Multicenter, Open Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of AT 1501 in Patients Undergoing Kidney Transplant

Conditions
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Kidney Transplant

Intervention / Treatment
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* Drug: AT-1501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Recipient of their first kidney transplant from a living or deceased donor Agree to comply with contraception requirements during and for at least 90 days after the last administration of study drug Exclusion Criteria: Induction therapy, other than study assigned rATG, planned as part of initial immunosuppressive regimen Currently treated with any systemic immunosuppressive regimen, including immunologic biologic therapies, with the exception of 5 mg prednisone or equivalent daily; Previous treatment with AT 1501 or any other anti CD40LG therapy The patient has previously received a bone marrow transplant or any other solid organ transplant, including a kidney, or will be undergoing a multi organ or dual kidney transplant Will receive a kidney with an anticipated cold ischemia time of > 30 hours; Will receive a kidney from a donor that meets any of the following: • Donation after Cardiac Death (DCD) criteria; or Extended Criteria Donor (ECD) criteria, defined as: Is blood group (ABO) incompatible; or Age ≥ 60 years; or Age 50-59 years with any 2 of the following criteria Death due to cerebrovascular accident History of hypertension Terminal creatinine ≥ 133 μmol/L Human leukocyte antigen identical (two haplotype match or zero HLA mismatch) donor Medical conditions that require chronic use of systemic steroids at a dose higher than 5 mg prednisone or equivalent per day History of a TE event, known hypercoagulable state, or condition requiring long term anticoagulation: Patients with a history of clotted venous access not requiring long term anticoagulation may be included at the Investigator's discretion if have no other history of TE events or known hypercoagulable state

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase 1b, open label, single-arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AT-1501 Single Arm<br>AT-1501 monoclonal antibody targeting CD40L given as an IV infusion | Drug: AT-1501<br>* Investigative Arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Incidences | Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and Adverse Events of Special Interest (AESIs) | Through study completion, an average up to 20 months | 
| Pharmacokinetic- PK profile | PK profile of the first dose of AT 1501 and at steady state Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (Ct), calculated using noncompartmental analysis (AUC0-t) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- Area under the plasma concentration | Area under the plasma concentration versus time curve from time 0 extrapolated to infinity, calculated using noncompartmental analysis (AUC0-inf) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- Cmax | Maximum observed plasma concentration (Cmax) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- Tmax | Time to reach maximum observed plasma concentration (Tmax) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- Ke | Terminal elimination rate constant (Ke) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- (t1/2) | Terminal phase half-life (t1/2) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- CL | Clearance (CL) | Day 1 and at steady state Month 3 | 
| Pharmacokinetic- (Vdss) | Volume of distribution at steady state (Vdss) | Day 1 and at steady state Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplant, Renal Allograft Rejection, Prophylaxis, AT-1501, CD40L inhibitor, Humanized blocking antibody to CD40L, Monoclonal Antibody, Renal, Transplant, ESRD, tegoprubart