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.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: ASP8597; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • St. Vincent Medical Center
    • San Diego, California, United States, 92123
      • Sharp Memorial
    • San Francisco, California, United States, 94143
      • University of California at San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • St. Barnabas Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17011
      • Pinnacle Health at Harrisburg
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Fort Worth, Texas, United States, 76104
      • Baylor All Saints Medical Center
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP8597 low dose	Drug: ASP8597; one time IV dose; Other Names: diannexin
Experimental: ASP8597 high dose	Drug: ASP8597; one time IV dose; Other Names: diannexin
Experimental: ASP8597 highest dose	Drug: ASP8597; one time IV dose; Other Names: diannexin
Placebo Comparator: Placebo; Placebo comparator used in Part 2 only	Drug: Placebo; one time IV dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: September 16, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): June 20, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: kidney transplant; ischemia-reperfusion injury; de novo kidney transplant; ASP8597; diannexin
• Other Study ID Numbers: 8597-CL-0201