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

Kidney Transplantation Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01442337
• Other study ID #: 8597-CL-0201
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: September 16, 2011
• Last updated: June 17, 2014
• Start date: December 2011
• Est. completion date: July 2013

Study information

• Verified date: June 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• ASP8597
one time IV dose
• Placebo
one time IV dose

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Montefiore Medical Center	Bronx	New York
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Baylor University Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Baylor All Saints Medical Center	Fort Worth	Texas
United States	East Carolina University	Greenville	North Carolina
United States	Pinnacle Health at Harrisburg	Harrisburg	Pennsylvania
United States	The Methodist Hospital	Houston	Texas
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	St. Vincent Medical Center	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	New York Presbyterian Hospital	New York	New York
United States	Sharp Memorial	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of California at San Francisco	San Francisco	California
United States	Washington University	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) variable for ASP8597: Maximum concentration (Cmax)	Part 1 PK variable	3 days	No
Primary	Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to last quantifiable concentration (AUClast)	Part 1 PK variable	3 days	No
Primary	Pharmacokinetic variable for ASP8597: Area under the concentration-time curve from time 0 to infinity (AUCinf)	Part 1 PK variable	3 days	No
Primary	Estimated glomerular filtration rate (eGFR) using abbreviated Modified Diet in Renal Disease (MDRD) formula - Part 2	Part 2 efficacy variable	12 months	No
Secondary	Pharmacokinetic variable for ASP8597: Time to attain Cmax (Tmax)	Part 1 PK variable	3 days	No
Secondary	Pharmacokinetic variable for ASP8597: Clearance (CL)	Part 1 PK variable	3 days	No
Secondary	Pharmacokinetic variable for ASP8597: Volume of Distribution (Vz)	Part 1 PK variable	3 days	No
Secondary	Pharmacokinetic variable for ASP8597: Apparent terminal elimination half-life (t1/2)	Part 1 PK variable	3 days	No
Secondary	Requirement of dialysis within the first 7 days post transplant - Part 1	Part 1 efficacy variable	7 days	No
Secondary	eGFR using abbreviated MDRD formula - Part 1	Part 1 efficacy variable	12 months	No
Secondary	Requirement of dialysis within the first 7 days post transplant - Part 2	Part 2 efficacy variable	7 days	No
Secondary	Patient survival	Part 2 efficacy variable	12 months	No
Secondary	Graft survival	Part 2 efficacy variable	12 months	No
Secondary	Biopsy-proven acute rejection (BPAR)	Part 2 efficacy variable	12 Months	No
Secondary	Clinically treated rejection	Subjects who receive immunosuppressive medications for the treatment of suspected or biopsy-proven acute rejection. Part 2 efficacy variable	12 months	No