Safety and Efficacy of Tegoprubart in Patients Undergoing Kidney Transplantation

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of AT-1501 compared with tacrolimus in patients undergoing kidney transplantation.

Detailed Description
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This study is a randomized, multicenter, open-label, active control study to evaluate the safety and efficacy of AT-1501 compared with tacrolimus in the prevention of rejection in patients undergoing kidney transplantation. Up to 120 de novo kidney transplant recipients will receive rATG induction with corticosteroids (CS), and mycophenolate as maintenance therapy, and will be randomized 1:1 to receive either AT-1501 or tacrolimus.

Official Title
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AT-1501-K207: BESTOW: A Phase 2, Multicenter, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Tegoprubart in Patients Undergoing Kidney Transplantation

Conditions
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Kidney Transplant Rejection

Intervention / Treatment
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* Drug: AT-1501
* Drug: Tacrolimus


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 Currently treated with corticosteroids other than topical or inhaled corticosteroids 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: 5a. Donation after Cardiac Death (DCD) criteria; Or 5b. Kidney Donor Profile Index (KDPI) of > 85%; Or 5c. Is blood group (ABO) incompatible Medical conditions that require chronic use of systemic corticosteroids or other immunosuppressants History of a thromboembolic event, known hypercoagulable state, or condition requiring long term anticoagulation Positive T- or B-cell crossmatch that is due to HLA antibodies or presence of a DSA at Screening

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigative<br>AT-1501 monoclonal antibody targeting CD40L given as an IV infusion | Drug: AT-1501<br>* IV infusions of AT-1501 20 mg/kg over 1 hour.<br>* Other names: Tegoprubart;|
| Active Comparator: Comparator<br>Tacrolimus administered BID, targeting a whole blood trough concentration of 6-12 ng/mL until Month 6, and 6-8 ng/mL thereafter | Drug: Tacrolimus<br>* Tacrolimus will be administered BID, targeting a whole blood trough concentration of 6-12 ng/mL until Month 6, and 6-8 ng/mL thereafter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| eGFR at 12 months | Estimated Glomerular Filtration Rate (eGFR) at 12 months post-transplant | Assessed from date of transplant through Day 364 (Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NODAT at 12 months post-transplant | The proportion of new onset diabetes after transplant (NODAT) at 12 months post-transplant | Assessed from date of transplant through Day 364 (Month 12 | 
| The proportion of patient and graft survival at 12 months post-transplant | Patient and graft survival are defined as either A) Death, B) re-transplantation or C) Requirement for regular dialysis | Assessed from date of transplant through Day 364 (Month 12) | 
| BPAR-free patient and graft survival at 12 months post-transplant | Assessed from date of transplant through Day 364 (Month 12) | The proportion of BPAR-free patient and graft survival at 12 months post-transplant | 
| BPAR at 12 months | The proportion of BPAR at 12 months | Assessed from date of transplant through Day 364 (Month 12) | 

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