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

This study has been terminated.
(Study was terminated by sponsor decision)
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01442337
First received: September 16, 2011
Last updated: June 17, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Kidney Transplantation
Drug: ASP8597
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacokinetic (PK) variable for ASP8597: Maximum concentration (Cmax) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to infinity (AUCinf) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Estimated glomerular filtration rate (eGFR) using abbreviated Modified Diet in Renal Disease (MDRD) formula - Part 2 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Part 2 efficacy variable


Secondary Outcome Measures:
  • Pharmacokinetic variable for ASP8597: Time to attain Cmax (Tmax) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Pharmacokinetic variable for ASP8597: Clearance (CL) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Pharmacokinetic variable for ASP8597: Volume of Distribution (Vz) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Pharmacokinetic variable for ASP8597: Apparent terminal elimination half-life (t1/2) [ Time Frame: 3 days ] [ Designated as safety issue: No ]
    Part 1 PK variable

  • Requirement of dialysis within the first 7 days post transplant - Part 1 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Part 1 efficacy variable

  • eGFR using abbreviated MDRD formula - Part 1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Part 1 efficacy variable

  • Requirement of dialysis within the first 7 days post transplant - Part 2 [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Part 2 efficacy variable

  • Patient survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Part 2 efficacy variable

  • Graft survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Part 2 efficacy variable

  • Biopsy-proven acute rejection (BPAR) [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    Part 2 efficacy variable

  • Clinically treated rejection [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Subjects who receive immunosuppressive medications for the treatment of suspected or biopsy-proven acute rejection. Part 2 efficacy variable


Enrollment: 21
Study Start Date: December 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ASP8597 low dose Drug: ASP8597
one time IV dose
Other Name: diannexin
Experimental: ASP8597 high dose Drug: ASP8597
one time IV dose
Other Name: diannexin
Experimental: ASP8597 highest dose Drug: ASP8597
one time IV dose
Other Name: diannexin
Placebo Comparator: Placebo
Placebo comparator used in Part 2 only
Drug: Placebo
one time IV dose

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01442337

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

No publications provided

Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01442337     History of Changes
Other Study ID Numbers: 8597-CL-0201
Study First Received: September 16, 2011
Last Updated: June 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
de novo kidney transplant
kidney transplant
ASP8597
diannexin
ischemia-reperfusion injury

ClinicalTrials.gov processed this record on August 27, 2014