QPI-1002 is being developed for prevention of acute kidney injury (AKI) in patients at risk for AKI following cardiac surgery and for reduction in the incidence and severity of delayed graft function after kidney transplantation. MedDRA version: 19.1 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: I5NP
Product Code: QPI-1002
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not applied
CAS Number: 1231737-88-4
Current Sponsor code: QPI-1002
Other descriptive name: I
Sponsors
Quark Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have the ability to understand the requirements of the study, are able to provide written informed consent (including consent for the use and disclosure of research related health information) and are willing and able to comply with the requirements of the study (including required study visits). 2. Male or female, age = 45 years old. 3. Have stable renal function per Investigator assessment and no known increase in serum creatinine of = 0.3 mg/dL (= 26.4 µmol/l) during preceding 4 weeks. 4. Scheduled to undergo non-emergent open chest cavity cardiovascular surgeries, including use of coronary pulmonary bypass (CPB) and no CPB: a. Combined coronary artery bypass grafting (CABG) surgery and surgery of one or more cardiac valve (valve(s) surgery) and at least 1 AKI Risk Factor; b. Surgery of more than one cardiac valve (valve surgery) and at least 1 AKI Risk Factor; c. Surgery of the aortic root or ascending part of the aorta, or aortic valve, including circulatory arrest and at least 1 AKI Risk Factor; d. Aortic root or ascending part of the aorta, combined with CABG and/or valve(s) surgery, including circulatory arrest and at least 1 AKI Risk Factor; e. If only CABG or single valve surgery, subjects are required to have at least 2 AKI Risk Factors: Note: TAVI/TAVR are allowed only if performed in combination with surgeries defined in Inclusion Criteria #4.AKI Risk Factors: • Age = 70 years • eGFR = 60 ml/min/1.73m2 by CKD-EPI formula at Screening. • Diabetes (Type 1 or 2), requiring at least 1 oral hypoglycemic agent or insulin • Proteinuria = 0.3g/d, spot UPCR = 0.3g/gm or urine dip stick = +2 • History of congestive heart failure requiring hospitalization 5. Are up-to-date on cancer screening according to site-specific pre-operative standard of care and past medical history must be negative for malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ or cervical carcinoma in situ. 6. A female subject is eligible to enter the study if she is: a. Not pregnant or nursing b. Of non-childbearing potential (i.e. post-menopausal defined as having been amenorrheic for at least l year prior to screening, or has had a bilateral tubal ligation at least 6 months prior to administration of study drug or bilateral oophorectomy or complete hysterectomy). c. If of childbearing potential, must have a negative serum pregnancy test within 48 hours prior to cardiac surgery and be using a highly effective means of contraception or using 2 methods of birth control concurrently, whichever is more stringent, which will be continued until the Day 90 visit. 7. A male subjects with female partners of childbearing potential must agree to use an effective means of contraception (per the site-specific guidelines or use 2 methods of birth control concurrently, whichever is more stringent), which will be continued until the Day 90 visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Have an eGFR = 20 mL/min/1.73 m2 2. Subjects with an eGFR = 60 mL/min/1.73 m2 requiring intravascular iodinated contrast within 48 hours of the day of surgery. However, subjects may be included if the post contrast increase in serum creatinine is 2 times the upper limit of normal (ULN) at time of screening 17. Have Child Pugh Class A liver disease with ALT/AST above the upper limit of normal or Class B or higher 18. Have a history or presence of a medical condition or disease or psychiatric condition that in the investigator’s assessment would render the subject ineligible for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the efficacy of a single intravenous (IV) infusion of QPI-1002 in preventing acute kidney injury (AKI) in subjects at high risk for AKI following cardiac surgery. • To assess the safety and tolerability of an IV infusion of QPI-1002 in comparison to placebo when administered to subjects at high risk for AKI following cardiac surgery. ;Secondary Objective: Not applicable ;Primary end point(s): Proportion of subjects developing AKI as defined by the AKIN criteria based on serum creatinine component only (Stage I, Stage II, or Stage III) through Day 5.;Timepoint(s) of evaluation of this end point: through Day 5 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of subjects developing at least one of the following events: death, needing renal replacement therapy (RRT) during the 90 day post-operative period, or having a = 25% reduction in SCr based eGFR at the Day 90 visit 2. Proportion of subjects developing at least one of the following events: death, needing RRT during the 90 day post-operative period, or having a = 25% reduction in S-cystatin C based eGFR at the Day 90 visit 3. Proportion of subjects developing at least one of the following events: AKI by the AKIN criteria of at least 3 days duration in which the initial serum creatinine increase occurs within 48 hours of the completion of the surgery or an increase in IL-18 level to = 90 pg/ml from baseline within 5 days in which the initial IL- 18 increase occurs within 48 hours of the completion of the surgery 4. Proportion of subjects developing AKI within 5 days post-surgery as defined by the AKIN (Acute Kidney Injury Network) scoring criteria a) overall (all stages combined), b) by stage 5. Proportion of subjects developing AKI within 5 days post-surgery as defined by the AKIN (Acute Kidney Injury Network scoring criteria by duration categories 6. Proportion of subjects developing AKI within 5 days post-surgery as defined by the RIFLE (Risk, Injury, Failure, Loss or ESRD) scoring criteria: a) overall (all stages combined), b) by stage 7. Proportion of subjects developing AKI within 5 days post-surgery as defined by the RIFLE (Risk, Injury, Failure, Loss or ESRD) scoring criteria by duration categories 8. Proportion of subjects developing AKI within 5 days post-surgery as defined by the KDIGO (Kidney Disease Improving Global Outcomes) scoring criteria: a) overall (all stages combined), b) by stage 9. Proportion of subjects developing AKI within 5 days post-surgery as defined by the KDIGO (Kidney Disease Improving Global Outcomes) scoring criteria by duration categories 10. Proportion of subjects developing AKI as defined by AKI | — |
Countries
Germany, United States
Contacts
Public ContactClinical Operations
Quark Pharmaceuticals, Inc.
Outcome results
None listed