Clinical trial NCT03403751: Phase 3 Study of Reltecimod vs Placebo in Patients With Sepsis-associated Acute Kidney Injury
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Kidney Injury
Peritonitis
Necrotizing Soft Tissue Infection
Keywords: Abdominal sepsis
AKI
NSTI
Lead sponsor: Atox Bio Ltd
Sponsor class: INDUSTRY
First posted: 2018-01-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization of study drug (Reltecimod) and placebo (normal saline)
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Freedom From Durable Loss of Renal Function at Day 28
timeFrame: 28 Days
measure: Serious Adverse Events (SAEs)
timeFrame: 28 Days
measure: Adverse Events (AEs)
timeFrame: 28 Days
Secondary outcomes:
measure: Freedom From Durable Loss of Renal Function at Day 14
timeFrame: 14 Days
measure: Intensive Care Unit (ICU)-Free Days
timeFrame: 28 Days
measure: Ventilator-free Days
timeFrame: 28 Days
measure: Vasopressor-free Days
timeFrame: 28 Days
measure: Hospital Days
timeFrame: 90 Days
measure: Cumulative Number of Deaths
timeFrame: 90 Days
measure: Secondary Infections
timeFrame: 28 Days
measure: ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category
timeFrame: 28 Days
measure: Ventilator-free Days by Day 14 mSOFA Category
timeFrame: 28 Days
measure: Vasopressor-free Days by Day 14 mSOFA Category
timeFrame: 28 Days
measure: Hospital Days by Day 14 mSOFA Category
timeFrame: 90 Days
measure: Hospital Discharge Location by Day 14 mSOFA Category
timeFrame: 90 Days
Other outcomes:
measure: Cumulative Mortality by Day 14 mSOFA Category
timeFrame: 90 Days
Locations:
city: Phoenix
country: United States
facility: Maricopa Medical Center
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Diego
country: United States
facility: UCSD Medical Center
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Medical Center
state: California
city: Colorado Springs
country: United States
facility: UCH-Memorial Health System
state: Colorado
city: Denver
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: LSU Health Science Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Trenton
country: United States
facility: Capital Health System, Inc.
state: New Jersey
city: Buffalo
country: United States
facility: Erie County Medical Center-Affliate of SUNYat Buffalo
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center (UCMC)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Hershey
country: United States
facility: The Pennsylvania State University and The Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Trauma Center at PENN
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC
state: South Carolina
city: Fort Worth
country: United States
facility: John Peter Smith Health Network
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Argenteuil
country: France
facility: Hopital Victor Dupouy
city: Brest
country: France
facility: CHRU la Cavale Blanche
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Dijon
country: France
facility: CHU Dijon
city: La Roche-sur-Yon
country: France
facility: CHD Vendee
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: Robert Salengro Hopital-CHRU Lille
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: CHU Lyon Sud
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Montpellier
country: France
facility: Hopital Saint Eloi
city: Nantes
country: France
facility: CHU de Nante Hotel-Dieu
city: Nîmes
country: France
facility: CHU Nimes
city: Paris
country: France
facility: Hopital Cochin
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: Nouvel Hopital Civil
Study officials:
affiliation: University of Florida Health
name: Azra Bihorac, MD
role: PRINCIPAL_INVESTIGATOR
References: