A Study to Evaluate the Effect of ASP8597 in Adult Kidney Transplant Patients
- Registration Number
- NCT01442337
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 21
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Subject is scheduled to receive a kidney transplant from a deceased donor meeting at least one of the following criteria:
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Expanded Criteria Donor (ECD)
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i Donor was > 60 years of age, OR
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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
-
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Donation after Cardiac Death (DCD) - Donor was pronounced dead prior to procurement of the kidney
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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
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Female subject is not pregnant and agrees to use an acceptable form of contraception throughout study
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Male subject agrees to use an adequate method of contraception and agrees to no sperm donation throughout the study
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ASP8597 low dose ASP8597 - ASP8597 high dose ASP8597 - Placebo Placebo Placebo comparator used in Part 2 only ASP8597 highest dose ASP8597 -
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) variable for ASP8597: Maximum concentration (Cmax) 3 days Part 1 PK variable
Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast) 3 days Part 1 PK variable
Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to infinity (AUCinf) 3 days Part 1 PK variable
Estimated glomerular filtration rate (eGFR) using abbreviated Modified Diet in Renal Disease (MDRD) formula - Part 2 12 months Part 2 efficacy variable
- Secondary Outcome Measures
Name Time Method Pharmacokinetic variable for ASP8597: Time to attain Cmax (Tmax) 3 days Part 1 PK variable
Pharmacokinetic variable for ASP8597: Clearance (CL) 3 days Part 1 PK variable
Pharmacokinetic variable for ASP8597: Volume of Distribution (Vz) 3 days Part 1 PK variable
Pharmacokinetic variable for ASP8597: Apparent terminal elimination half-life (t1/2) 3 days Part 1 PK variable
Requirement of dialysis within the first 7 days post transplant - Part 1 7 days Part 1 efficacy variable
eGFR using abbreviated MDRD formula - Part 1 12 months Part 1 efficacy variable
Requirement of dialysis within the first 7 days post transplant - Part 2 7 days Part 2 efficacy variable
Patient survival 12 months Part 2 efficacy variable
Graft survival 12 months Part 2 efficacy variable
Biopsy-proven acute rejection (BPAR) 12 Months Part 2 efficacy variable
Clinically treated rejection 12 months Subjects who receive immunosuppressive medications for the treatment of suspected or biopsy-proven acute rejection. Part 2 efficacy variable
Trial Locations
- Locations (19)
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
St. Vincent Medical Center
🇺🇸Los Angeles, California, United States
Sharp Memorial
🇺🇸San Diego, California, United States
New York Presbyterian Hospital
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of California at San Francisco
🇺🇸San Francisco, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Washington University
🇺🇸St. Louis, Missouri, United States
St. Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Pinnacle Health at Harrisburg
🇺🇸Harrisburg, Pennsylvania, United States
The Methodist Hospital
🇺🇸Houston, Texas, United States
Baylor All Saints Medical Center
🇺🇸Fort Worth, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States