Study of APX-115 in Contrast Induced Acute Kidney Injury in Subjects Undergoing PCI
- Conditions
- Contrast Induced Acute Kidney Injury
- Interventions
- Drug: PlaceboDrug: Isuzinaxib (APX-115)
- Registration Number
- NCT05758896
- Lead Sponsor
- Aptabio Therapeutics, Inc.
- Brief Summary
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 280 patients will be randomized into the study in a 1:1 ratio to 400 mg APX-115 (Isuzinaxib hydrochloride) or placebo arm.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 280
- Willing and able to provide informed consent.
- 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.
- Diagnosed with coronary artery disease.
- Planned to undergo coronary angiography within 4 weeks of being consented.
- Risk of CKD evidenced by 30 mL/min/1.73m2 ≤ eGFR (Glomerular filtration rate) < 90 mL/min/1.73 m2 confirmed by local or central laboratory.
- 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.
- 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.
- Females who are pregnant or who are planning to become pregnant before the end of planned enrolment or who are breastfeeding.
- Subjects who are not expected to go through PCI at the discretion of investigator or cardiologist
- Subjects who have a history of hypersensitivity to contrast media or who cannot be administered contrast media according to investigator's discretion
- Acute myocardial infarction within 1 month prior to Screening
- ESRD confirmed by eGFR < 15 mL/min/1.73 m2 at Screening.
- 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.
- 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).
- Known or suspected hypersensitivity to any component of the APX-115 formulation.
- History of acute kidney injury or renal dialysis within 1 month prior to Screening and/or plan to undergo a renal dialysis during enrolment.
- Clinically apparent liver disease as determined by the Investigator (e.g., jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis) or moderate or severe hepatic impairment as determined by Child-Pugh score (Class B or C) at Screening.
- Impaired liver function, defined as alanine aminotransferase (ALT) ≥ 2.5 times UNL or Total bilirubin >1.5 × ULN, unless the subject has known Gilbert's syndrome.
- Any sign or symptom of acute or chronic infection at Screening.
- Receipt of any investigational drug within 4 weeks prior to Screening.
- Confirmed or suspected abuse of alcohol or controlled substances within 1 year prior to Screening.
- Clinically significant hematology abnormalities; hemoglobin <9 g/dL for females or <11 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.
- 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.
- Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation with protocol requirements
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 4 x Placebo capsules administered QD, orally, for 5 consecutive days Isuzinaxib (APX-115) 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
- Primary Outcome Measures
Name Time Method Safety endpoints: adverse event Day -2 to day 84 Number of adverse events
Safety endpoints: labs Day 0 to day 84 Number of abnormal results of Hematology, Biochemistry and Urinalysis
Safety endpoints: vital sign Day 0 to day 84 Number of subjects with abnormal Vital Signs
Safety endpoints: ECG Day 0 to day 84 Abnormal Electrocardiogram (ECG)
Safety endpoints: physical exam Day 0 to day 84 Abnormal physical examination
- Secondary Outcome Measures
Name Time Method pharmacokinetics parameters: peak concentration (Cmax, Tmax) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: apparent total clearance (CL/F) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
Incidence rate of Acute kidney injury from baseline up to 72 hours after PCI procedure 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
pharmacokinetics parameters: renal clearance (CLR) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: apparent nonrenal clearance (CLNR/F) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
Kidney function parameters: creatinine, BUN over 12-week period Serum creatinine and BUN level
pharmacokinetics parameters: steady state peak plasma concentration (Css,max) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
Long term kidney function: Serum creatinine week 4 and week 12 Serum creatinine level
Long term kidney function: eGFR week 4 and week 12 eGFR level
Kidney function parameters: eGFR over 12-week period eGFR using CKD-EPI
pharmacokinetics parameters: the area under the plasma concentration-time curve (AUC0-last, AUCtau) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: steady state trough plasma concentration (Css,min) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: apparent volume of distribution (V/F) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: fraction/cumulated fraction of excreted in urine Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: steady state after 5 consecutive days of drug administration Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
pharmacokinetics parameters: terminal half-life (t1/2) Day -2~2 to be assessed from plasma and urine samples (subset of subjects only)
Trial Locations
- Locations (14)
Sarkis Clinical Trials
🇺🇸Ocala, Florida, United States
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Inje University Ilsan Paik Hospital
🇰🇷Goyang, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Kangwon National University Hospital
🇰🇷Chuncheon, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Kangbuk Samsung Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea St. Vincent's Hospital
🇰🇷Suwon, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Florida Cardiovascular Research
🇺🇸Hialeah, Florida, United States