A Study to Evaluate the Safety and Efficacy of AC607 for the Treatment of Kidney Injury in Cardiac Surgery Subjects (ACT-AKI)

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of AC607 for the Treatment of Acute Kidney Injury in Cardiac Surgery Subjects

Subjects entering the study will have undergone cardiac surgery. Those who experience kidney injury within 48 hours of their surgery will be enrolled into the study. Once enrolled, subjects will receive a single administration of AC607 or placebo. Kidney recovery will be evaluated over the subsequent 30 days and death or the need for dialysis will be evaluated within 90 days of dosing. After 90 days (evaluation period), subjects will enter a 3-year extension phase of the study to monitor safety and long-term outcomes (follow-up period).

Study Overview

• Status: Terminated
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Biological: AC607; Biological: Vehicle Only

Detailed Description

The study will enroll post-cardiac surgery subjects (CABG and/or valve) with laboratory evidence of AKI within 48 hrs of removal from cardiopulmonary bypass. Subjects will be randomly assigned (1:1 ratio) to treatment with a single administration of AC607 or placebo (approximately 100 subjects per group).

Safety and efficacy assessments will be performed daily during the post-operative hospital stay from the day randomized into the study until discharge, at 30 days, and at 90 days after study drug administration (evaluation phase). Safety and long-term clinical outcomes will be assessed at 6, 12, 24 and 36 months (long-term follow-up phase).

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • University of Manitoba - St. Boniface Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • CDHA Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • McMaster - Hamilton General Hospital / TAARI
    • London, Ontario, Canada, N6J 1S1
      • London Health Sciences Centre, University Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Diego, California, United States, 92103
      • University of California, San Diego
    • Stanford, California, United States, 94305-2299
      • Stanford Hospital and Clinics
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Washington Hospital Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Robert Wood Johnson Medical School
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • UTHealth, The University of Texas Health Science Center at Houston
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - Renal Services
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • CAMC Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 21 years
• Had cardiovascular surgery utilizing cardiopulmonary bypass
• Have a pre-operative (baseline) serum creatinine value collected within 30 days of surgery (if multiple laboratory results are available within this time window, the most recent serum creatinine value prior to surgery will be used to establish the baseline)
• Willing and able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up
• Ability to give informed consent or have a legally acceptable representative do so for them
• Have AKI defined as ≥ 0.5 mg/dL rise in serum creatinine from baseline within 48 hours of removal from cardiopulmonary bypass

Exclusion Criteria:

• Active cancer and/or receiving active treatment for cancer, with the exception of squamous cell or basal cell carcinoma of the skin
• Had surgery for thoraco-abdominal aortic aneurysm (TAAA)
• Currently participating in another interventional drug or device clinical study
• Prisoner or other detainee
• Has a current medical condition that would preclude or compromise femoral artery catheter placement
• Has an intra-aortic balloon pump (IABP) in place within 2 hours of catheter placement
• Has a ventricular assist device (VAD) or extracorporeal membrane oxygenation (ECMO) in place at the time of the study catheter placement
• Prior history of solid organ or bone marrow transplant
• Stage 5 CKD or currently on dialysis
• Are expected to receive dialysis within 24 hours of enrollment or dosing
• Had a complication during surgery or post-operatively that, in the opinion of the principal investigator (PI), significantly increases the risk of complications to the subject and therefore precludes dosing the subject
• Are pregnant or lactating. A woman with child-bearing potential may be tested for pregnancy at the discretion of the PI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: AC607; Treatment with AC607	Biological: AC607; AC607 will be a single administration at a target dose of 2 x 10E6 hMSC/kg body weight; Other Names: stem cells; allogeneic bone marrow-derived human mesenchymal
PLACEBO_COMPARATOR: Placebo; Treatment with Placebo	Biological: Vehicle Only; The dose will be calculated and recorded in the same way as for AC607.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Kidney Recovery defined as a post-operative serum creatinine return to pre-operative baseline values.	The first occurrence of a post-dosing serum creatinine level that is equal to or less than the subject's pre-operative baseline level.	Within 30 days of dosing.

Secondary Outcome Measures

Outcome Measure	Time Frame
All-Cause Mortality or Dialysis (composite endpoint).	Subjects who died or received dialysis within 30 and 90 days after dosing.

Collaborators and Investigators

• Sponsor: AlloCure Inc.
• Investigators: Study Director: Viken Paragamian

Publications and helpful links

General Publications

• Zhao L, Hu C, Zhang P, Jiang H, Chen J. Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury. J Cell Mol Med. 2019 Feb;23(2):720-730. doi: 10.1111/jcmm.14035. Epub 2018 Nov 28.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (ESTIMATE): May 21, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 6, 2014
• Last Update Submitted That Met QC Criteria: August 5, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Acute renal failure; Acute Kidney Injury; Human mesenchymal stem cells; Allogeneic stem cells
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: AC 6071103