Clinical trial NCT01442337: A Study to Evaluate the Effect of ASP8597 in Adult Kidney Transplant Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Kidney Transplantation
Keywords: de novo kidney transplant
kidney transplant
ASP8597
diannexin
ischemia-reperfusion injury
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2011-09-28
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Pharmacokinetic (PK) variable for ASP8597: Maximum concentration (Cmax)
timeFrame: 3 days
measure: Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)
timeFrame: 3 days
measure: Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: 3 days
measure: Estimated glomerular filtration rate (eGFR) using abbreviated Modified Diet in Renal Disease (MDRD) formula - Part 2
timeFrame: 12 months
Secondary outcomes:
measure: Pharmacokinetic variable for ASP8597: Time to attain Cmax (Tmax)
timeFrame: 3 days
measure: Pharmacokinetic variable for ASP8597: Clearance (CL)
timeFrame: 3 days
measure: Pharmacokinetic variable for ASP8597: Volume of Distribution (Vz)
timeFrame: 3 days
measure: Pharmacokinetic variable for ASP8597: Apparent terminal elimination half-life (t1/2)
timeFrame: 3 days
measure: Requirement of dialysis within the first 7 days post transplant - Part 1
timeFrame: 7 days
measure: eGFR using abbreviated MDRD formula - Part 1
timeFrame: 12 months
measure: Requirement of dialysis within the first 7 days post transplant - Part 2
timeFrame: 7 days
measure: Patient survival
timeFrame: 12 months
measure: Graft survival
timeFrame: 12 months
measure: Biopsy-proven acute rejection (BPAR)
timeFrame: 12 Months
measure: Clinically treated rejection
timeFrame: 12 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: St. Vincent Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Harrisburg
country: United States
facility: Pinnacle Health at Harrisburg
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor All Saints Medical Center
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Astellas Pharma Global Development
name: Medical Director
role: STUDY_DIRECTOR
References: