A Study to Evaluate the Effect of ASP8597 in Adult Kidney Transplant Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and tolerability of a single intravenous dose of ASP8597 in kidney transplant recipients.

Detailed Description
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This is a two-part study. Part 1 (Phase 2) has completed enrollment. Subjects are currently being followed per protocol. Data from Part 1 will be used to determine the doses used in Part 2 (Phase 3). Part 2 will enroll approximately 573 subjects and is planned to have 2 doses of ASP8597 (low dose and either the high or highest dose) along with placebo.

Official Title
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A Phase 2/3, Double-Blind, Placebo-Controlled, Two-Part Study (Part 1 Open-Label) to Assess the Safety, Efficacy and Pharmacokinetics of Single Intravenous Doses of ASP8597 (Diannexin) in de Novo Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: ASP8597
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is scheduled to receive a kidney transplant from a deceased donor meeting at least one of the following criteria: Expanded Criteria Donor (ECD) i Donor was > 60 years of age, OR ii. Donor was 50-59 years of age, inclusive, and met at least two of the following criteria: Donor died of a cerebral bleed Donor had a history of hypertension Donor's terminal serum creatinine concentration was > 1.5 mg/dL Donation after Cardiac Death (DCD) - Donor was pronounced dead prior to procurement of the kidney Standard Criteria Donor (SCD) i. Donor with terminal serum creatinine < 1.5 mg/dL where kidney is anticipated to have a minimum of 24 hours of cold ischemia prior to transplantation, OR ii. Donor with terminal serum creatinine > 1.5 mg/dL and any cold ischemic time up to exclusion limit Female subject is not pregnant and agrees to use an acceptable form of contraception throughout study Male subject agrees to use an adequate method of contraception and agrees to no sperm donation throughout the study Exclusion Criteria: Female subject is pregnant or lactating Donor kidney is anticipated to have more than 40 hours of cold ischemia time Donor is > 66 years of age Donor meets both DCD and ECD criteria Subject has previously received, or is receiving an organ transplant other than a kidney Subject has a positive T or B cell crossmatch by the investigational site's standard method of determination. For recipients where only a flow cytometry crossmatch is performed and is positive in either T or B cell testing, recipients are excluded only if donor specific, anti-HLA antibody is detected by flow cytometry based, specific anti-HLA antibody testing Subject has ABO blood type incompatibility with his/her organ donor Recipient or donor is known by medical history to be seropositive for human immunodeficiency virus (HIV) Subject has a known bleeding diathesis Subject has a International Normalized Ratio (INR) > 1.5 times upper limit of normal at Screening Subject has a platelet count < 100,000 platelets/µL at Screening Subject used anti-platelet agents [e.g., Plavix® (clopidogrel bisulfate), Brilinta® (ticagrelor)] (with the exception of aspirin < 100 mg/day for cardiovascular prophylaxis), anti-coagulants [e.g., Pradaxa® (dabigatran), Xarelto® (rivaroxaban)], anti-thrombotics, and/or blood-thinning agents within the 10 days prior to Screening; and/or subject is expected to require use of any of these agents during the first 15 days of the study period (with the exception of standard of care peri-operative administration of heparin for DVT prophylaxis) Subject has an uncontrolled concomitant infection Subject has a current malignancy or a history of any malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully Subject currently is participating in an investigational drug study, or participated in an investigational drug study within the last 30 days) Subject has a history of or is believed to have used an illicit drug(s) and/or abused alcohol within the last 3 months Subject has an unstable psychiatric illness Subject has previously received ASP8597 or participated in a study involving ASP8597

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP8597 low dose<br> | Drug: ASP8597<br>* one time IV dose<br>* Other names: diannexin;|
| Experimental: ASP8597 high dose<br> | Drug: ASP8597<br>* one time IV dose<br>* Other names: diannexin;|
| Experimental: ASP8597 highest dose<br> | Drug: ASP8597<br>* one time IV dose<br>* Other names: diannexin;|
| Placebo Comparator: Placebo<br>Placebo comparator used in Part 2 only | Drug: Placebo<br>* one time IV dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) variable for ASP8597: Maximum concentration (Cmax) | Part 1 PK variable | 3 days | 
| Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast) | Part 1 PK variable | 3 days | 
| Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to infinity (AUCinf) | Part 1 PK variable | 3 days | 
| Estimated glomerular filtration rate (eGFR) using abbreviated Modified Diet in Renal Disease (MDRD) formula - Part 2 | Part 2 efficacy variable | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic variable for ASP8597: Time to attain Cmax (Tmax) | Part 1 PK variable | 3 days | 
| Pharmacokinetic variable for ASP8597: Clearance (CL) | Part 1 PK variable | 3 days | 
| Pharmacokinetic variable for ASP8597: Volume of Distribution (Vz) | Part 1 PK variable | 3 days | 
| Pharmacokinetic variable for ASP8597: Apparent terminal elimination half-life (t1/2) | Part 1 PK variable | 3 days | 
| Requirement of dialysis within the first 7 days post transplant - Part 1 | Part 1 efficacy variable | 7 days | 
| eGFR using abbreviated MDRD formula - Part 1 | Part 1 efficacy variable | 12 months | 
| Requirement of dialysis within the first 7 days post transplant - Part 2 | Part 2 efficacy variable | 7 days | 
| Patient survival | Part 2 efficacy variable | 12 months | 
| Graft survival | Part 2 efficacy variable | 12 months | 
| Biopsy-proven acute rejection (BPAR) | Part 2 efficacy variable | 12 Months | 
| Clinically treated rejection | Subjects who receive immunosuppressive medications for the treatment of suspected or biopsy-proven acute rejection. Part 2 efficacy variable | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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de novo kidney transplant, kidney transplant, ASP8597, diannexin, ischemia-reperfusion injury