A Dose Escalation and Safety Study of I5NP to Prevent Acute Kidney Injury (AKI) in Patients at High Risk of AKI Undergoing Major Cardiovascular Surgery (QRK.004)

• Status: Terminated
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, randomized, double-blind, dose escalation, safety and pharmacokinetic study. The study will be conducted in approximately 10 sites in the United States. Up to 48 patients at high risk for AKI (CCF score ≥ 5 OR an estimated GFR (eGFR) <60 mL/min/1.73 m2) who have undergone major cardiovascular surgery will participate. Patients will receive a single IV injection of I5NP or placebo following cardiovascular surgery. I5NP will be administered 4 hours (+/- 30 minutes) following removal of the cardiopulmonary bypass machine (CBM).

The duration of the study is approximately 44 days, inclusive of a 14 day screening period. Patients will be contacted by phone at 6 and 12 months for follow-up questions. Patient visits are screening, day of surgery, hospital in-patient Days 1, 2, 3 - 5 and Day 7 or hospital discharge. Safety follow-up will continue until 30 days post-surgery. 2 phone calls will be made at 6 and 12 months after date of surgery.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Quark Pharmaceuticals

Criteria

Inclusion Criteria (before surgery):

• Patient age between 21 years and 85 years old

• Patient is capable of giving consent

• Patient is willing and able to comply with the visit schedule and study procedures including post-hospitalization discharge follow-up

• Patient is undergoing any major cardiac or vascular surgery requiring the use of cardiopulmonary bypass machine (CBM)

• Patient has a cumulative score of ≥ 5 on the Cleveland Clinic Foundation (CCF) Acute Kidney Injury (AKI) risk factor scale OR the patient has an estimated GFR (eGFR) <60 mL/min/1.73 m2, as determined from the simplified (4-variable) MDRD (Modification of Diet in Renal Disease) equation at the time of the Screening/Baseline examination

• The patient reports that they are up to date and have had normal findings on their age- and sex-appropriate cancer screening, per American Cancer Society guidelines, for breast cancer, cervical cancer, rectal cancer, and prostate cancer. If a patient is not up to date, the relevant screening test must be performed and a normal result documented prior to dosing.

Inclusion Criteria (during surgery):

• Patient must have been on cardiopulmonary bypass machine (CBM)

Inclusion Criteria (after surgery):

• Patient must be in the ICU for dosing to facilitate study procedures including PK blood draws and PK urine sampling

Exclusion Criteria (before surgery):

• Patient has had cancer or may be predisposed due to a family history of:

• a clinical syndrome predisposing to malignancy, such as Familial Polyposis Coli, Von Hippel Landau disease (associated with renal cell cancers and renal cysts) and Li-Fraumeni syndrome (associated with inherited mutations of the p53 tumor-suppressor gene)

• the same malignancy in two or more first- or second-degree relatives

• Patient has a history of any abnormality on chest X-ray that could represent a malignancy

• Patient has a clinically significantly elevated pancreatic and/or hepatic enzyme level, defined as any grade 2, 3 or 4 value according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 3.0

• Women of childbearing potential are to be excluded from this study. Every female subject is considered of childbearing potential unless she has had sterilization surgery, or is post-menopausal.

• Women 21-59, post-menopausal is defined as no menses for at least 12 months and an elevated follicle stimulating hormone (FSH) level.

• Women 60-85, post-menopausal is defined as no menses in at least 12 months.

• Patient has participated in a study of an experimental therapy in the last 30 days

• Patient is currently receiving immunosuppressive therapy [this criterion does NOT apply to topical steroids and inhalation steroids for chronic obstructive pulmonary disease (COPD) and/or asthma]

• Pre-operative extracorporeal membrane oxygenation

• Patient has Intra-Arterial Balloon Pump (IABP) or other Left Ventricular Assist Device (LVAD)

• Evidence that patient is experiencing possible AKI prior to surgery, defined as a > 1.5 times increase in serum creatinine from screening to any time prior to surgery

• Patient has comfort measures only or do not resuscitate (DNR) status

• Patient is participating in a concurrent interventional study

• Patient has received intravenous contrast material < 24 hours prior to surgery

• In the opinion of the investigator a pre-operative concomitant disease or clinical/laboratory finding that significantly raises the risk of complications in the post-operative period and therefore precludes dosing of the patient

Exclusion Criteria (during surgery):

• In the opinion of the investigator, an intra-operative complication has occurred that significantly raises the risk of complications in the post operative period and therefore precludes dosing of the patient

Exclusion Criteria (after surgery):

• In the opinion of the investigator, a complication has occurred in the post-operative period at any time prior to dosing that significantly raises the risk of further complications and therefore precludes dosing of the patient