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

Acute Kidney Injury Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03403751
• Other study ID #: ATB-203
• Status: Terminated
• Phase: Phase 3
• Start date: May 24, 2018
• Est. completion date: December 14, 2019

Study information

• Verified date: September 2021
• Source: Atox Bio Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: December 14, 2019
• Est. primary completion date: December 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Necrotizing Soft Tissue Infection
• Peritonitis
• Sepsis
• Soft Tissue Infections
• Wounds and Injuries

Intervention

Drug:
• 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
• Placebo
Single IV infusion of 0.5 mL/kg of 0.9% saline (volume equivalent to Reltecimod dosing schema) over approximately 10 minutes

Locations

Country	Name	City	State
France	Hopital Victor Dupouy	Argenteuil
France	CHRU la Cavale Blanche	Brest
France	CHU Clermont-Ferrand	Clermont-Ferrand
France	CHU Dijon	Dijon
France	CHD Vendee	La Roche-sur-Yon
France	CH Le Mans	Le Mans
France	Robert Salengro Hopital-CHRU Lille	Lille
France	CHU de Limoges	Limoges
France	CHU Lyon Sud	Lyon
France	Hopital Edouard Herriot	Lyon
France	Hopital Saint Eloi	Montpellier
France	CHU de Nante Hotel-Dieu	Nantes
France	CHU Nimes	Nîmes
France	Hopital Cochin	Paris
France	CHU Rennes	Rennes
France	Nouvel Hopital Civil	Strasbourg
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	St. Luke's University Health Network	Bethlehem	Pennsylvania
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Erie County Medical Center-Affliate of SUNYat Buffalo	Buffalo	New York
United States	MUSC	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Cincinnati Medical Center (UCMC)	Cincinnati	Ohio
United States	UCH-Memorial Health System	Colorado Springs	Colorado
United States	University of Missouri	Columbia	Missouri
United States	The Ohio State University	Columbus	Ohio
United States	University of Colorado Hospital	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	John Peter Smith Health Network	Fort Worth	Texas
United States	UF Health Shands Hospital	Gainesville	Florida
United States	East Carolina University	Greenville	North Carolina
United States	The Pennsylvania State University and The Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	LSU Health Science Center	New Orleans	Louisiana
United States	The Trauma Center at PENN	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Maricopa Medical Center	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California, Davis Medical Center	Sacramento	California
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSD Medical Center	San Diego	California
United States	Harborview Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Harbor-UCLA Medical Center	Torrance	California
United States	Capital Health System, Inc.	Trenton	New Jersey
United States	Banner University Medical Center	Tucson	Arizona
United States	Washington Hospital Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Atox Bio Ltd

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cumulative Mortality by Day 14 mSOFA Category	Percentage of patients who died through Day 90 using life table analysis	90 Days
Primary	Freedom From Durable Loss of Renal Function at Day 28	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
Primary	Serious Adverse Events (SAEs)	Number of patients experiencing at least one SAE	28 Days
Primary	Adverse Events (AEs)	The number of patients experiencing at least one AE.	28 Days
Secondary	Freedom From Durable Loss of Renal Function at Day 14	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
Secondary	Intensive Care Unit (ICU)-Free Days	ICU-free days refers to the number of days a patient did not spend time in the ICU through Day 28.	28 Days
Secondary	Ventilator-free Days	Ventilator-free days refers to the number of days a patient was not on a ventilator through Day 28.	28 Days
Secondary	Vasopressor-free Days	Vasopressor-free days refers to the number of days a patient did not receive a vasopressor through Day 28.	28 Days
Secondary	Hospital Days	Hospital days refers to the number of days a patient spent time in the hospital.	90 Days
Secondary	Cumulative Number of Deaths	The number of deaths occurring through Day 90	90 Days
Secondary	Secondary Infections	Number of patients experiencing at least one secondary infection	28 Days
Secondary	ICU-free Days by Day 14 Modified Sequential Organ Failure Assessment (mSOFA) Category	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
Secondary	Ventilator-free Days by Day 14 mSOFA Category	The number of days a patient was not on a ventilator through Day 28, by mSOFA category	28 Days
Secondary	Vasopressor-free Days by Day 14 mSOFA Category	The number of days a patient was not receiving a vasopressor through Day 28, by mSOFA category	28 Days
Secondary	Hospital Days by Day 14 mSOFA Category	The number of days a patient was in the hospital.	90 Days
Secondary	Hospital Discharge Location by Day 14 mSOFA Category	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