Phase 3 Study of Reltecimod vs Placebo in Patients With Sepsis-associated Acute Kidney Injury

September 17, 2021 updated by: Atox Bio Ltd

Phase 3 Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Reltecimod as Compared to Placebo in Addition to Standard of Care in Patients With Sepsis-associated Acute Kidney Injury (SA-AKI)

Phase 3 multicenter study to be conducted in up to 90 qualified participating sites globally to assess the efficacy and safety of Reltecimod vs placebo in patients with sepsis-associated Stage 2/3 AKI.

Study Overview

Detailed Description

Phase 3 randomized, placebo controlled study assessing the efficacy (complete recovery from AKI) and safety of Reltecimod in patients with suspected or confirmed abdominal sepsis (planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures for control of underlying abdominal infection within 24 hours of evaluation by medical personnel) or patients with surgically confirmed necrotizing soft tissue infection (NSTI), requiring intensive care unit (ICU) or step down unit admission and in whom the diagnosis of Stage 2/3 acute kidney injury (AKI; as defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria) is established at initial presentation for medical evaluation or up to 48 hours from the suspected diagnosis of abdominal sepsis or from surgically confirmed diagnosis of NSTI.

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Argenteuil, France
        • Hôpital Victor Dupouy
      • Brest, France
        • CHRU La Cavale Blanche
      • Clermont-Ferrand, France
        • Chu Clermont-Ferrand
      • Dijon, France
        • CHU Dijon
      • La Roche-sur-Yon, France
        • CHD Vendee
      • Le Mans, France
        • CH Le Mans
      • Lille, France
        • Robert Salengro Hopital-CHRU Lille
      • Limoges, France
        • Chu de Limoges
      • Lyon, France
        • Hôpital Edouard Herriot
      • Lyon, France
        • CHU Lyon Sud
      • Montpellier, France
        • Hopital Saint Eloi
      • Nantes, France
        • CHU de Nante Hotel-Dieu
      • Nîmes, France
        • CHU Nîmes
      • Paris, France
        • Hôpital Cochin
      • Rennes, France
        • CHU Rennes
      • Strasbourg, France
        • Nouvel Hopital Civil
    • Arizona
      • Phoenix, Arizona, United States, 85008
        • Maricopa Medical Center
      • Tucson, Arizona, United States, 24857
        • Banner University Medical Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Medical Center
      • Sacramento, California, United States, 95817
        • University of California, Davis Medical Center
      • San Diego, California, United States, 92103
        • UCSD Medical Center
      • Torrance, California, United States, 90502
        • Harbor-UCLA Medical Center
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • UCH-Memorial Health System
      • Denver, Colorado, United States, 80045
        • University of Colorado Hospital
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale New Haven Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Hospital Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Health Shands Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospital and Clinics
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University Of Kentucky
    • Louisiana
      • New Orleans, Louisiana, United States, 70012
        • LSU Health Science Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • Minnesota
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center-Fairview
    • Missouri
      • Columbia, Missouri, United States, 65211
        • University of Missouri
    • New Jersey
      • Trenton, New Jersey, United States, 98638
        • Capital Health System, Inc.
    • New York
      • Buffalo, New York, United States, 14215
        • Erie County Medical Center-Affliate of SUNYat Buffalo
    • North Carolina
      • Charlotte, North Carolina, United States, 28208
        • Carolinas Medical Center
      • Greenville, North Carolina, United States, 27834
        • East Carolina University
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center (UCMC)
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18015
        • St. Luke's University Health network
      • Hershey, Pennsylvania, United States, 17033
        • The Pennsylvania State University and the Milton S. Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Philadelphia, Pennsylvania, United States, 19104
        • The Trauma Center at PENN
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC
    • Texas
      • Fort Worth, Texas, United States, 76104
        • John Peter Smith Health Network
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Has either suspected or documented diagnosis of abdominal sepsis requiring treatment with parenteral antibiotics and planned or completed surgical (laparotomy or laparoscopy) or interventional radiologic procedures within 24 hours of evaluation by medical personnel. Recommended surgical or interventional radiologic procedures be performed with 12 hours of evaluation by medical personnel.
  2. Initial diagnosis of AKI Stage 2 or 3 according to KDIGO AKI criteria established either upon presentation to medical care in those patients with suspected abdominal sepsis or in those patients in whom the initial diagnosis of AKI is established during the 48 hour period from the suspected diagnosis of abdominal sepsis.
  3. Study medication must be administered within 6 hours of confirmation of onset of Stage 2 or 3 AKI as established at the study site, under the following criteria:

    • After the decision is made by the attending surgeon at the study site for a surgical or interventional radiology procedure for the abdominal infection OR
    • After confirmed diagnosis of abdominal infection has been established by a surgical or interventional radiology procedure

Exclusion Criteria:

  1. Has known prior history of chronic kidney disease (CKD( with a documented estimated GFR (eGFR) < 30 mL/min

    • Exception: Patients with history of CKD but no available prior eGFR who have documented normal kidney size on ultrasound or computed tomography evaluation (performed within 90 days of screening) will be eligible

  2. Patients receiving renal replacment therapy (RRT) for CKD
  3. . Previously diagnosed with documented AKI in the last 30 days
  4. Documented primary glomerular disease or toxic tubulo-interstitial nephritis at the time of AKI diagnosis
  5. Patient is not expected to survive throughout 28 days of study due to significant underlying medical condition
  6. Any concurrent medical condition, which in the opinion of the Investigator, may compromise the safety of the patient or the objectives of the study or the patient will not benefit from treatment such as:

    • Congestive heart failure (CHF) {New York Heart Association (NYHA) class III-IV}
    • Severe chronic obstructive pulmonary disease (COPD) {GOLD - Global Initiative for Chronic Obstructive Lung Disease - stage IV. or chronic hypoxemia)
    • Liver dysfunction {Childs-Pugh class C}
    • Primary or acquired immunodeficiency or immunosuppression due to treatment with immunosuppressive medications
    • Known HIV infection with CD4 count < 200 cells/mm3 or < 14% of all lymphocytes
    • Neutropenia < 1,000 cells/mm3 not due to the underlying infection
    • Receiving or about to receive chemotherapy or biologic anti-cancer treatment,
    • Hematological and lymphatic malignancies in the last 5 years
  7. Patient has acute pancreatitis with no established source of infection, uncomplicated appendicitis, or cholangitis or cholecystitis without peritonitis;
  8. Pregnant or lactating women
  9. Concurrent or previous enrollment in a clinical trial involving investigational drug or a medical device

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Reltecimod 0.5 mg/kg
Single IV infusion of Reltecimod 0.5 mg/kg
Single IV infusion of 0.5 mg/kg Reltecimod (at a concentration of 1 mg/mL) over approximately 10 minutes
Other Names:
  • AB103 0.5 mg/kg
Placebo Comparator: Placebo
Single IV infusion of 0.9% Sodium Chloride Injection (Normal Saline)
Single IV infusion of 0.5 mL/kg of 0.9% saline (volume equivalent to Reltecimod dosing schema) over approximately 10 minutes
Other Names:
  • 0.9% Sodium Chloride Injection (Normal saline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom From Durable Loss of Renal Function at Day 28
Time Frame: 28 Days
Freedom from durable loss of renal function at Day 28 required all of the following 3 components: alive at Day 28, free of dialysis at Day 28, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 28 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).
28 Days
Serious Adverse Events (SAEs)
Time Frame: 28 Days
Number of patients experiencing at least one SAE
28 Days
Adverse Events (AEs)
Time Frame: 28 Days
The number of patients experiencing at least one AE.
28 Days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Freedom From Durable Loss of Renal Function at Day 14
Time Frame: 14 Days
Freedom from durable loss of renal function at Day 14 required all of the following 3 components: alive at Day 14, free of dialysis at Day 14, and less than 37% loss of estimated glomerular filtration rate (eGFR) at Day 14 from patient reference eGFR (measured by Modification of Diet in Renal Disease [MDRD] formula).
14 Days
Intensive Care Unit (ICU)-Free Days
Time Frame: 28 Days
ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.
28 Days
Ventilator-free Days
Time Frame: 28 Days
Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.
28 Days
Vasopressor-free Days
Time Frame: 28 Days
Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.
28 Days
Hospital Days
Time Frame: 90 Days
Hospital days refers to the number of days a patient spent time in the hospital.
90 Days
Cumulative Number of Deaths
Time Frame: 90 Days
The number of deaths occurring through Day 90
90 Days
Secondary Infections
Time Frame: 28 Days
Number of patients experiencing at least one secondary infection
28 Days
ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category
Time Frame: 28 Days
The number of days a patient did not spend in the ICU through Day 28, by mSOFA category (mSOFA total score of 1 or less; mSOFA total score of 2 or more). Modified Sequential Organ Failure Assessment (mSOFA) total scores range from 0 to 20, with higher scores reflecting a worse clinical status or outcome. An mSOFA total score of 0 or 1 reflects resolution of organ dysfunction/failure.
28 Days
Ventilator-free Days by Day 14 mSOFA Category
Time Frame: 28 Days
The number of days a patient was not on a ventilator through Day 28, by mSOFA category
28 Days
Vasopressor-free Days by Day 14 mSOFA Category
Time Frame: 28 Days
The number of days a patient was not receiving a vasopressor through Day 28, by mSOFA category
28 Days
Hospital Days by Day 14 mSOFA Category
Time Frame: 90 Days
The number of days a patient was in the hospital.
90 Days
Hospital Discharge Location by Day 14 mSOFA Category
Time Frame: 90 Days
Number of patients with more favorable discharge location (home or rehabilitation facility) or less favorable discharge location (skilled nursing facility, another acute care facility, death, other) among patients alive at Day 14.
90 Days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Mortality by Day 14 mSOFA Category
Time Frame: 90 Days
Percentage of patients who died through Day 90 using life table analysis
90 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Azra Bihorac, MD, University of Florida Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2018

Primary Completion (Actual)

December 14, 2019

Study Completion (Actual)

December 14, 2019

Study Registration Dates

First Submitted

January 6, 2018

First Submitted That Met QC Criteria

January 11, 2018

First Posted (Actual)

January 19, 2018

Study Record Updates

Last Update Posted (Actual)

October 12, 2021

Last Update Submitted That Met QC Criteria

September 17, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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