Study of APX-115 in Contrast Induced Acute Kidney Injury in Subjects Undergoing PCI

Effect on Contrast Induced Acute Kidney Injury of APX-115 in Subjects Undergoing Percutaneous Coronary Intervention A Randomized, Double-blind, Parallel Group, Multicenter, Multi-national Trial

This phase 2 study is to assess the safety and efficacy of APX-115 active doses in Contrast Induced Acute Kidney Disease compared to placebo following multiple oral dosing in patients with undergoing percutaneous coronary intervention. It is anticipated that approximately 230 patients will be randomized into the study in a 1:1 ratio to 400 mg APX-115 (Isuzinaxib hydrochloride) or placebo arm.

Study Overview

• Status: Active, not recruiting
• Conditions: Contrast Induced Acute Kidney Injury
• Intervention / Treatment: Drug: Isuzinaxib (APX-115); Drug: Placebo

Detailed Description

Patients with chronic kidney disease undergoing percutaneous coronary intervention deserve careful consideration of various clinical options to minimize the risk of contrast-induced acute kidney injury and to optimize clinical outcomes. Contrast-induced acute kidney injury (CI-AKI) is a leading cause of a hospital-acquired renal failure and has been reported to affect both the mortality and morbidity of patients receiving contrast media. Contrast-induced acute kidney injury is the third leading cause of hospital-acquired acute kidney injury and has been recognized as a serious complication of percutaneous coronary intervention (PCI), which may be associated with increased morbidity and mortality.

APX-115 is a potent small molecule inhibitor of NADPH-oxidase (NOX) isozymes developed by AptaBio Therapeutics, Inc. In-vivo study results suggest that multiple NOX isoforms may contribute to renal injury in CI-AKI model, and pan-NOX inhibition may be a new therapeutic approach for prevention of CI-AKI.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Korea
  • Chuncheon, South Korea
    • Kangwon National University Hospital
  • Daegu, South Korea
    • Keimyung University Dongsan Hospital
  • Daejeon, South Korea
    • Chungnam National University Hospital
  • Goyang, South Korea
    • Inje University Ilsan Paik Hospital
  • Gwangju, South Korea
    • Chonnam National University Hospital
  • Seongnam-si, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Kangbuk Samsung Hospital
  • Seoul, South Korea
    • Korea University Anam Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Suwon, South Korea
    • The Catholic University Of Korea St. Vincent's Hospital
  • Ulsan, South Korea
    • Ulsan University Hospital
• United States
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Scott & White Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide informed consent.
2. Male or female, of any race or ethnicity, 18 years of age or older, inclusive, on the day of informed consent. Racial and ethnic minorities should be included in the study population to the greatest extent possible.
3. Diagnosed with coronary artery disease.
4. Planned to undergo coronary angiography within 4 weeks of being consented.
5. 30 mL/min/1.73m2 ≤ eGFR (Glomerular filtration rate) < 90 mL/min/1.73 m2 confirmed by local or central laboratory.
6. Women of childbearing potential or males willing and able to use at least one protocol-specified method of contraception for the duration of their enrolment.
7. Subject is aware of the investigational nature of this study and willing to comply with protocol treatments, blood tests, and other evaluations listed in the ICF.

Exclusion Criteria:

1. Females who are pregnant or who are planning to become pregnant before the end of planned enrolment or who are breastfeeding.
2. Subjects who are not expected to go through PCI at the discretion of investigator or cardiologist
3. Subjects who have a history of hypersensitivity to contrast media or who cannot be administered contrast media according to investigator's discretion
4. Acute myocardial infarction within 1 month prior to Screening
5. CKD stage 4 and 5 confirmed by eGFR < 30 mL/min/1.73 m2 at Screening.
6. Clinically significant heart disease as determined by the Investigator within 2 months prior to Screening including but not limited to any of following; cardiogenic shock, treatment requiring intra-aortic balloon pump (IABP) support, treatment with extra corporeal membrane oxygenation (ECMO), or NYHA class IV heart failure.
7. Uncontrolled treated/untreated hypertension (defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg, mean of measured 2 times at Screening will be permitted).
8. Known or suspected hypersensitivity to any component of the APX-115 formulation.
9. History of acute kidney injury or renal dialysis within 1 month prior to Screening and/or plan to undergo a renal dialysis during enrolment.
10. Clinically apparent liver disease as determined by the Investigator or moderate or severe hepatic impairment as determined by Child-Pugh score (Class B or C) at Screening.
11. Impaired liver function, defined as alanine aminotransferase (ALT) > 2.5 times UNL and Total bilirubin >1.5 × ULN, unless the subject has known Gilbert's syndrome.
12. Any sign or symptom of acute or chronic infection at Screening.
13. Receipt of any investigational drug within 4 weeks prior to Screening.
14. Confirmed or suspected abuse of alcohol or controlled substances within 1 year prior to Screening.
15. Clinically significant hematology abnormalities; hemoglobin <9 g/dL for females or <10 g/dL for males, absolute neutrophil count <1500/mm3, platelet count <100 × 109/L) at Screening. If any parameter is below the specified threshold, one hematology retest analyzed at the central or local laboratory within a week prior to randomization is permitted with the result of the last sample being conclusive.
16. Any other clinically significant medical condition or laboratory abnormality as determined by the Investigator that might jeopardize the safety of the subject, impair subject compliance, or impede safety/efficacy observations during enrolment.
17. Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation with protocol requirements
18. Use of CYP1A2, CYP2B6 and CYP3A4 substrates or UGT inhibitors and inducers or OAT3 substrates prior to enrollment or concurrently. It will be only accepted to be eligible to screening if the subjects' concomitant medications will be reviewed and approved by the medical monitor and/or sponsor prior to the initial study dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isuzinaxib (APX-115); 4 x Isuzinaxib 88 mg calculated as free base (4 x 100mg APX-115(Isuzinaxib hydrocloride) capsules as salt form) administered QD, orally, for 5 consecutive days	Drug: Isuzinaxib (APX-115); Treatment allocation in 1:1 ratio to Isuzinaxib or Placebo; Other Names: Isuzinaxib Hydrochloride
Placebo Comparator: Placebo; 4 x Placebo capsules administered QD, orally, for 5 consecutive days	Drug: Placebo; Treatment allocation in 1:1 ratio to Isuzinaxib or Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety endpoints: adverse event	Number of adverse events	Day -2 to day 84
Safety endpoints: vital sign	Number of subjects with abnormal Vital Signs	Day 0 to day 84
Safety endpoints: physical exam	Abnormal physical examination	Day 0 to day 84
Safety endpoints: ECG	Abnormal Electrocardiogram (ECG)	Day 0 to day 84
Safety endpoints: labs	Number of abnormal results of Hematology, Biochemistry and Urinalysis	Day 0 to day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of Acute kidney injury	definition of CI-AKI: Serum Creatinine absolute variation ≥ 0.5mg/dL or Serum creatinine relative variation increasing 25% from baseline up to 72 hours after CAG with the exposure of contrast medium and PCI	from baseline up to 72 hours after PCI procedure
Long term kidney function: Serum creatinine	Serum creatinine level	week 4 and week 12
Long term kidney function: eGFR	eGFR level	week 4 and week 12
Kidney function parameters: creatinine, BUN	Serum creatinine and BUN level	over 12-week period
Kidney function parameters: eGFR	eGFR using CKD-EPI	over 12-week period
pharmacokinetics parameters: the area under the plasma concentration-time curve (AUC0-last, AUCtau)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: peak concentration (Cmax, Tmax)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: steady state peak plasma concentration (Css,max)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: steady state trough plasma concentration (Css,min)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: steady state after 5 consecutive days of drug administration	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: apparent total clearance (CL/F)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: renal clearance (CLR)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: apparent nonrenal clearance (CLNR/F)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: apparent volume of distribution (V/F)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: terminal half-life (t1/2)	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
pharmacokinetics parameters: fraction/cumulated fraction of excreted in urine	to be assessed from plasma and urine samples (subset of subjects only)	Day -2~2
Adverse event in patients with eGFR < 45 mL/min/1.73m2	Number of adverse events	Day -2 to day 84
Vital signs in patients with eGFR < 45 mL/min/1.73m2	number of subjects with abnormal vital signs	Day 0 to day 84
Number of subjects with eGFR < 45 mL/min/1.73m2 with clinically significant findings on physical examination	The number of subjects within the specified subgroup who exhibit clinically significant abnormal findings based on investigator's physical examination will be assessed over time.	Day 0 to day 84
Number of subjects with eGFR < 45 mL/min/1.73m2 with normal or abnormal electrocardiogram (ECG) results	The number of subjects within the specified subgroup who exhibit normal or abnormal ECG findings will be assessed over time.	Day 0 to day 84
Labs in patients with eGFR < 45 mL/min/1.73m2	Number of abnormal results of hematology, biochemistry and urinalysis	Day 0 to day 84

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers assessment	NGAL, KIM-1, Cystatin-C and NT-proBNP	72 hours
Composite PCI outcome	death, myocardial infarction (MI) and stent thrombosis (ST)	over 12-week period

Collaborators and Investigators

• Sponsor: Aptabio Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Percutaneous Coronary Intervention; Acute Kidney Injury; Contrast media; ROS; Isuzinaxib; APX-115
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; isuzinaxib
• Other Study ID Numbers: A01-115-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No