Long-Term Safety and Efficacy of Tegoprubart in Kidney Transplant Recipients

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

Detailed Description
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This is a multicenter, open-label, active control extension study to assess the long-term safety and efficacy of AT-1501 (tegoprubart) compared with tacrolimus in the preservation of allograft function after kidney transplantation. The number of patients enrolled for OLE study will depend on the enrollment in the Parent studies. To be eligible for participation in this study, participants must have completed a designated Parent study. Participants in this study will continue the treatment regimen they were receiving in the Parent study. Dose regimens will include either AT-1501 (tegoprubart) or tacrolimus.

Official Title
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AT-1501-K209: BESTOW-EXTENSION: A Phase 2, Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Tegoprubart in Kidney Transplant Recipients

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: Successfully completed qualifying Parent study, where entry into the OLE was offered; Continue to be able to understand the key components of the study as described in the written ICF, and is willing and able to provide written informed consent; Agree not to participate in another interventional study while on treatment; If female, is surgically sterile or 2 years postmenopausal. Women of childbearing potential may be enrolled if a pregnancy test is negative at baseline. Women of childbearing potential and men with partners that are of childbearing potential must agree to use highly effective methods of contraception from baseline, through 90 days after the last administration of the study drug. Examples of acceptable methods of contraception are described in Table 6. If male, agree to use a medically accepted highly effective method of contraception and agree to use this method for 90 days after last administration of the study drug and agree to not donate sperm for 90 days after last administration of the study drug. Exclusion Criteria: Unwilling or unlikely to comply with the study requirements, in the opinion of the Investigator; Met any of the stopping criteria or discontinued study drug in the Parent study; Pregnant or breastfeeding.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AT-1501<br>AT-1501 20 mg/kg administered every 3 weeks IV + MMF 1000 mg per os (orally) (PO) twice daily (BID) or MPS 720 mg PO BID + Corticosteroids 5 mg of prednisone PO once daily (QD) or equivalent | Drug: AT-1501<br>* AT-1501 20 mg/kg administered every 3 weeks IV + MMF 1000 mg PO twice daily (BID) or MPS 720 mg PO BID + Corticosteroids 5 mg of prednisone PO once daily (QD) or equivalent<br>* Other names: Tegoprubart;|
| Active Comparator: Tacrolimus<br>Tacrolimus dosed PO BID with the dose titrated to maintain a trough concentration of 6-8 ng/mL+ MMF 1000 mg PO BID or MPS 720 mg PO BID + Corticosteroids 5 mg of prednisone PO QD or equivalent | Drug: Tacrolimus<br>* Tacrolimus dosed PO BID with the dose titrated to maintain a trough concentration of 6-8 ng/mL+ MMF 1000 mg PO BID or MPS 720 mg PO BID + Corticosteroids 5 mg of prednisone PO QD or equivalent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability - Incidence of Treatment Emergent Adverse Events | Incidence of treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events (TEAEs), and treatment-emergent AEs of special interest (TEAEoSI). | Assessed from date of enrollment through Month 48 | 
| Safety and Tolerability - Kidney Transplant Medication Side Effects | Kidney transplant medication side effects using the Modified Transplant Symptom Occurrence and Symptom Distress Scale-59 (MTSOSD) at baseline and 12, 24, 36, and 48 months. | Assessed from date of enrollment through Month 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patient and graft survival at 12, 24, 36, and 48 months | A participant is considered to have graft functional impairment if they have an eGFR <60 mL/min/1.73m^2. | Assessed from date of enrollment through Month 48 | 
| The proportion of participants with Graft function impairment at 12, 24, 36, and 48 months | A participant is considered to have graft functional impairment if they have an eGFR <60 mL/min/1.73m^2. | Assessed from date of enrollment through Month 48 | 
| Proportion of participants with BPAR at 12, 24, 36, and 48 months | The Proportion of participants with BPAR at 12, 24, 36, and 48 months. | Assessed from date of enrollment through Month 48 | 
| Proportion of composite endpoint (graft failure, BPAR, or death) at 12, 24, 36, and 48 months | The Proportion of participants with composite endpoint (graft failure, BPAR, or death) at 12, 24, 36, and 48 months. | Assessed from date of enrollment through Month 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplant, AT-1501, Renal Allograft Rejection, Prophylaxis, CD40L Inhibitor, Humanized blocking antibody to CD40L, monoclonal antibody, renal, transplant, ESRD, tegoprubart