Overview

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