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

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

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.

Eligibility Criteria:
Inclusion Criteria:

* Subject is scheduled to receive a kidney transplant from a deceased donor meeting at least one of the following criteria:

  1. 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:

       1. Donor died of a cerebral bleed
       2. Donor had a history of hypertension
       3. Donor's terminal serum creatinine concentration was \> 1.5 mg/dL
  2. Donation after Cardiac Death (DCD) - Donor was pronounced dead prior to procurement of the kidney
  3. 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