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

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

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.

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