Clinical trial NCT06374797: A Study of Auxora in Patients With AKI and Injurious Lung "Crosstalk"
Official title: Auxora for the Treatment of AKI and Modulation of Injurious "Crosstalk" With the Lung: A Randomized Control Trial (KOURAGE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: AKI
Acute Kidney Injury
Auxora
Lead sponsor: CalciMedica, Inc.
Sponsor class: INDUSTRY
First posted: 2024-04-19
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Approximately 150 patients with acute kidney injury (AKI) associated with acute hypoxemic respiratory failure (AHRF) will be randomized at up to 40 sites. Patients will be randomly assigned to either Auxora or matching placebo. Study drug infusions will occur every 24 hours for five consecutive days for a total of five infusions.

Detailed description: This double blind, randomized, placebo-controlled study will evaluate the efficacy, safety, and tolerability of Auxora in patients with severe AKI who have associated AHRF. The definition of AKI and the stages of AKI will be based on the classification system proposed by the Acute Kidney Injury Working Group of Kidney Disease: Improving Global Outcomes (KDIGO) and incorporate both serum creatinine and urine volume criteria. AHRF will be defined as a P/F ≤ 300 that has been determined by either an arterial blood gas or imputed from the oxygen saturation (SpO2) recorded using pulse oximetry and is being treated with high flow nasal cannula with minimum flow rate ≥ 30 liters/min, or non-invasive mechanical ventilation, or invasive mechanical ventilation. Approximately 150 patients with severe AKI, defined as having developed either stage 2 or 3 AKI at the time of consent, who have associated AHRF will be randomized 1:1 into either the Auxora or placebo group using a computer-generated randomization scheme accessed through an interactive voice/web response system (IXRS). Randomization will be stratified by the use of invasive mechanical ventilation and by Stage 3 AKI.

Patients who are randomized to the Auxora group will receive 1.25 mL/kg (2.0 mg/kg of zegocractin) IV over 4 hours at 0 hours and then 1.0 mL/kg (1.6 mg/kg of zegocractin) IV over 4 hours at 24, 48, 72, and 96 hours for a total of 5 doses. Patients who are randomized to the placebo group will receive 1.25 mL/kg IV over 4 hours at 0 hours and then 1.0 mL/kg IV over 4 hours at 24, 48, 72, and 96 hours for a total of 5 doses. Placebo will be a matching emulsion without the active pharmaceutical ingredient zegocractin. The sponsor, investigators, pharmacists, and patients will be blinded to the assigned group. The Start of First Infusion of Study Drug (SFISD) should occur no more than 24 hours of the patient or legally authorized representative (LAR) providing informed consent. A study physician or appropriately trained delegate will perform study-specific hospital assessments immediately prior to the SFISD, and then every 24 hours after the SFISD until 720 hours (Day 30), or until discharge if earlier. All patients, including those that are discharged from the hospital to home, or to a skilled nursing facility, or to an extended care facility, will be assessed at Day 90.

All AKI should be managed according to the KDIGO 2012 guidelines which recommends maintaining adequate organ perfusion, avoiding volume overload, avoiding hyperglycemia, discontinuing nephrotoxic agents, and adjusting dosing of renally excreted medications. AHRF/acute respiratory distress syndrome (ARDS) should be managed according to the 2023 European Society of Intensive Care Medicine (ESICM) major recommendations.

Eligibility criteria: Inclusion Criteria:

1. The patient is ≥ 18 years of age.
2. The patient has developed Stage 2 or Stage 3 AKI.
3. The patient has a documented partial pressure of oxygen \[Pa02\]/fraction of inspired oxygen \[FiO2\] (P/F) ≤ 300 in the prior 24 hours, either imputed from SpO2 or obtained from an arterial blood gas, that is not explained by cardiogenic pulmonary edema or volume overload
4. The patient is being treated with either high flow nasal cannula with minimum flow rate ≥ 30 liters/min, or non-invasive mechanical ventilation, or invasive mechanical ventilation at time of randomization.
5. A female patient of childbearing potential who is sexually active with a male partner is willing to practice acceptable methods of birth control for 30 days after the last dose of study drug.
6. A male patient who is sexually active with a female partner of childbearing potential is willing to practice acceptable methods of birth control for 30 days after the last dose of study drug. A male patient must not donate sperm for 30 days after the last dose of study drug.
7. The patient is willing and able to, or has a legally authorized representative (LAR) who is willing and able to, provide informed consent to participate and to cooperate with all aspects of the protocol.

Exclusion Criteria:

1. The patient has a do not intubate directive.
2. The patient has chronic lung disease that requires supplemental non-invasive oxygen as an outpatient or home mechanical ventilation. The use of non-invasive mechanical ventilation to treat obstructive sleep apnea is not an exclusion.
3. The patient has been hospitalized in the ICU for more than 10 days.
4. The patient has been receiving invasive mechanical ventilation for \> 120 hours.
5. The patient is receiving extracorporeal membrane oxygen (ECMO).
6. The patient has started or is planned to start kidney replacement therapy (KRT) before randomization.
7. The patient has a serum triglyceride level ≥ 500 mg/dL.
8. The patient has a direct bilirubin level \>3.0 mg/dL or both a direct bilirubin level ≥ 2.0 mg/dL and an international normalized ratio (INR) ≥ 1.7.
9. AKI is suspected to be secondary to: renal artery or renal vein thrombosis; hepato-renal syndrome; cholesterol emboli syndrome; acute glomerulonephritis; vasculitis; acute allergic interstitial nephritis; intrarenal or extrarenal urinary tract obstruction; use of immune checkpoint inhibitor.
10. The patient has a known history of an organ transplant.
11. The patient has a known history of HIV infection.
12. The patient has known history of hepatitis B infection.
13. The patient is currently receiving chemotherapy.
14. The patient is currently receiving immunosuppressive medications
15. The patient is known to be pregnant or is currently nursing.
16. The patient is allergic to eggs.
17. The patient is currently participating in another study of an investigational drug

Primary outcomes:
measure: Days alive, ventilator-free and kidney replacement therapy (KRT)-free from SFISD through Day 30
timeFrame: SFISD through Day 30
Secondary outcomes:
measure: Major adverse kidney event (MAKE) 90-1: ≥25% decline in estimated glomerular filtration rate (eGFR) from baseline, incident KRT, and all-cause mortality at 90 days
timeFrame: At Day 90
measure: MAKE 90-2: ≥35% decline in eGFR from baseline, incident KRT, and all-cause mortality at 90 days
timeFrame: At Day 90
measure: Proportion of patients alive at Day 30
timeFrame: At Day 30
measure: Proportion of patients alive at Day 90
timeFrame: Day 90
measure: Days alive and ventilator-free from start of first infusion of study drug (SFISD) through Day 30
timeFrame: SFISD through Day 30
measure: Days alive and KRT-free from SFISD through Day 30
timeFrame: SFISD through Day 30
measure: Proportion of patients recovered from AHRF through Day 30 as categorized by an 8-point ordinal scale
timeFrame: SFISD through Day 30
measure: Proportion of patients receiving KRT at Day 30
timeFrame: At Day 30
measure: Proportion of patients receiving KRT at Day 90
timeFrame: At Day 90
measure: Number of patients with treatment-related adverse events (TEAE)
timeFrame: SFISD through Day 90
measure: Number of patients with grade 3 TEAEs
timeFrame: SFISD through Day 90
Other outcomes:
measure: Days alive and not hospitalized through Day 30
timeFrame: SFISD through Day 30
measure: Proportion of patients re-hospitalized through Day 30
timeFrame: SFISD through Day 30
measure: Proportion of patients re-hospitalized through Day 90
timeFrame: SFISD through Day 90
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Chandler
country: United States
facility: Chandler Regional Hospital
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: Torrance
country: United States
facility: Torrance Memorial Medical Center
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at UCLA-Harbor Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Washington DC
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Sarasota
country: United States
facility: Sarasota Memorial
state: Florida
city: Tampa
country: United States
facility: Tampa General
state: Florida
city: Johns Creek
country: United States
facility: Emory Johns Creek Hospital
state: Georgia
city: Boise
country: United States
facility: St Luke's Hospital
state: Idaho
city: Chicago
country: United States
facility: Northwestern University-Pulmonary & Critical Care Medicine
state: Illinois
city: Indianapolis
country: United States
facility: University of Indiana
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Brigham & Woman's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford
state: Michigan
city: Midland
country: United States
facility: My Michigan Health
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Hannibal
country: United States
facility: Hannibal Regional
state: Missouri
city: Brooklyn
country: United States
facility: NYU Langone Health - Brooklyn
state: New York
city: New Hyde Park
country: United States
facility: Northshore University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Health - Bellview
state: New York
city: New York
country: United States
facility: NYU Langone Health - Tisch Hospital
state: New York
city: Queens
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: UT Houston
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: CalciMedica, Inc.
name: Sudarshan Hebbar, MD, Chief Medical Officer
role: STUDY_DIRECTOR
References: