Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury (AKI) Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery

NCT ID: NCT03941483

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 351 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2021-10-20

Brief Summary

The purpose of this study was to evaluate the efficacy of postsurgery treatment with ASP1128 in subjects at risk for AKI following CABG and/or valve surgery.

This study also investigated the safety and tolerability of postsurgery treatment with ASP1128, and pharmacokinetic characteristics of ASP1128 in subjects at risk for AKI following CABG and/or valve surgery.

Detailed Description

The study comprised of a screening visit, followed by CABG and/or valve surgery on Day 1, double-blind treatment period and a follow-up period up to Day 90 in subjects with moderate/severe risk of AKI at 2-22 hours post-surgery.

Subjects with low risk of AKI at 2-22 hours post-surgery assessment were enrolled in the observational cohort to evaluate subject characteristics and biomarkers for exploratory objectives.

Conditions

Acute Kidney Injury (AKI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ASP1128

Participants received ASP1128 solution administered by 15 minutes intravenous infusion with in 24 hours after the end of surgery and thereafter once daily for 2 days.

Group Type: EXPERIMENTAL

ASP1128

Intervention Type: DRUG

Intravenous Infusion

Matching placebo

Participants received placebo matched to ASP1128 solution administered by 15 minutes intravenous infusion with in 24 hours after the end of surgery and thereafter once daily for 2 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous Infusion

Observational cohort

Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 nanogram per milliliter (ng/mL)\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

ASP1128

Intravenous Infusion

Intervention Type: DRUG

Placebo

Intravenous Infusion

Intervention Type: DRUG

Other Intervention Names

MA-0217

Eligibility Criteria

Inclusion Criteria

• Subject agrees not to participate in another interventional study after signing the informed consent form and until the end of study (EoS) visit has been completed.
• Subject is ≥ 35 years of age at the time of screening (visit 1).
• Subject undergoing non-emergent open chest cardiovascular surgery with the use of cardiopulmonary bypass pump (CPB) (i.e., coronary artery bypass graft (CABG) and/or valve surgery [including aortic root and ascending aorta surgery without circulatory arrest]) within 4 weeks of screening (visit 1).
• Subject is at risk of developing acute kidney injury (AKI) following cardiovascular surgery, i.e., has 1 or more of the following AKI risk factors:

• Age at screening of ≥ 70 years
• Documented history of eGFR < 60 mL/min per 1.73 m^2 as per Modification of Diet in Renal Disease Study (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (or documented measured glomerular filtration rate assessment) (history needs to be present for at least 90 days prior to screening, and eGFR at screening or baseline needs to be < 60 mL/min per 1.73 m^2, as well as per CKD-EPI equation.)
• Documented history of congestive heart failure requiring hospitalization. This condition should exist for ≥ 90 days prior to screening.
• Documented history of diabetes mellitus (type 1 or 2) of ≥ 90 days prior to screening, and subject is on active antidiabetic medication treatment for ≥ 90 days.
• Documented history of proteinuria/albuminuria at any time point before screening (urinary dipstick result of ≥ 2+, documented urinary albumin creatinine ratio measurement of ≥ 300 mg/g, or documented total quantity of protein in a 24-hour urine collection test ≥ 0.3 g/day)
• Subject must have the ability and willingness to return for all scheduled visits and perform all assessments.
• Female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

• Not a woman of childbearing potential (WOCBP), OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 30 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 30 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 30 days after the final study drug administration.
• Male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 30 days after the final study drug administration.
• Male subject must not donate sperm during the treatment period and for at least 30 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 30 days after the final study drug administration.

Exclusion Criteria

At Screening:

• Subject has received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Subject has received RRT within 30 days prior to screening.
• Subject has CKD stage 4 or 5, or stage 3 (i.e., eGFR 30-59 mL/min per 1.73m^2) with a known history of eGFR < 30 mL/min per 1.73 m^2 as per CKD-EPI or MDRD equation within 6 months prior to screening.
• Subject has a prior kidney transplantation.
• Subject has a known or suspected glomerulonephritis (other than Diabetic Kidney Disease).
• Subject has confirmed or treated endocarditis or other current active infection requiring antibiotic treatment within 30 days prior to screening.
• Subject is using prohibited.
• Subject has a prior history of intravenous drug abuse within 1 year prior to screening.
• Subject has a known chronic liver disorder with Child-Pugh B or C classification.
• Subject has any of the following abnormal liver or kidney function parameters:

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) or bilirubin increased to > 1.5 times the ULN.
• eGFR < 30 mL/min per 1.73 m^2 as per CKD-EPI equation.
• Subject has use of left ventricular assist device, intra-aortic balloon pump or other cardiac devices, or catecholamines within 7 days prior to screening.
• Subject has surgery scheduled to be performed without CPB (i.e., "Off-Pump" surgery).
• Subject has surgery scheduled to be performed under conditions of circulatory arrest, including planned deep hypothermic circulatory arrest.
• Subject has surgery scheduled for aortic dissection.
• Subject has surgery for a condition that is immediately life-threatening.
• Subject has surgery scheduled to correct major congenital heart defect.
• Subject has current or previous malignant disease. Subjects with a history of cancer are considered eligible if the subject has undergone therapy and the subject has been considered disease free or progression free for at least 5 years. Subject with completely excised basal cell carcinoma or squamous cell carcinoma of the skin and completely excised cervical cancer in situ are also considered eligible.

Preoperatively on the Day of Surgery:

• Subject has AKI (any stage) present at presurgery baseline.
• Subject has known or suspected infection/sepsis at time of presurgery baseline.

• Subject requires Extracorporeal Membrane Oxygenation during or after completion of surgery.
• Subject requires ventricular assist device during or after completion of surgery.
• Subject has surgery performed "Off-Pump" at any time during surgery.

General:

• Subject has other condition, which makes the subject unsuitable for study participation.
• Female subject who is pregnant or lactating or has a positive pregnancy test within 72 hours prior to screening and/or randomization, has been pregnant within 6 months before screening assessment or breastfeeding within 3 months before screening or who is planning to become pregnant within the total study period.
• Subject has a known or suspected hypersensitivity to ASP1128 or any components of the formulation used.

• Minimum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Senior Director

Role: STUDY_DIRECTOR

Astellas Pharma Inc

Locations

Heart Center Research, LLC

Huntsville, Alabama, United States

Sarver Heart Center

Tucson, Arizona, United States

Morton Plant Hospital

Clearwater, Florida, United States

Health Park Medical Center

Fort Myers, Florida, United States

Shands Hospital

Gainesville, Florida, United States

Florida Hospital Pepin Heart Institute

Tampa, Florida, United States

Southern Illinois University

Springfield, Illinois, United States

Luthern Medical Group

Fort Wayne, Indiana, United States

IU Health - Methodist

Indianapolis, Indiana, United States

St. Vincent Heart Center

Indianapolis, Indiana, United States

Indiana University Health Ball Memorial Hospital

Muncie, Indiana, United States

MercyOne Iowa Heart Center

Des Moines, Iowa, United States

Delmarva Heart, LLC

Salisbury, Maryland, United States

Ascension Genesys Hospital

Grand Blanc, Michigan, United States

Mid Michigan Medical Center

Midland, Michigan, United States

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Baptist Medical Center

Jackson, Mississippi, United States

St. Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Lourdes Cardiology Services

Voorhees Township, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

Moses H. Cone Memorial Hospital

Greensboro, North Carolina, United States

Fairview Hospital - Cleveland Clinic

Cleveland, Ohio, United States

ProMedica Toledo Hospital

Toledo, Ohio, United States

Vanderbilt University

Nashville, Tennessee, United States

Baylor Scott & White Heart Hospital

Plano, Texas, United States

University of Texas Health Science Center

San Antonio, Texas, United States

WVU Heart and Vascular Institute

Morgantown, West Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=14509&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website

https://www.clinicaltrials.astellas.com/study/1128-CL-0201/

Link to results and other applicable study documents on the Astellas Clinical Trials website

Other Identifiers

1128-CL-0201

Identifier Type: -

Identifier Source: org_study_id