A Dose Escalation and Safety Study of I5NP in Patients Undergoing Major Cardiovascular Surgery

Phase 1

Completed

• Conditions: Injury of Kidney; Acute Renal Failure
• Interventions: Drug: I5NP (a small interfering RNA); Drug: placebo

• Registration Number: NCT00554359
• Lead Sponsor: Quark Pharmaceuticals

Brief Summary

This is a Phase 1, randomized, double-blind, dose escalation, safety and pharmacokinetic study. The study will be conducted in approximately 8-10 centers in the United States and Switzerland. Up to 32 patients 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 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.

Detailed Description

The drug (I5NP) is a small interfering RNA that is being developed to protect patients from acute kidney injury after cardiac bypass surgery. This first-in-man study will test the safety of I5NP and measure how long the drug stays in the blood stream after injection. This study is not meant to test if I5NP protects kidneys from the damage that may occur in rare cases during surgery. Another purpose of this dose escalation study is to find out the right dose of the experimental drug to be given to study subjects in future studies. Even though there were no harmful effects seen in the animals tested, we do not know what side effects the experimental drug might cause in humans.

Study Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-11-04
• Study First Submitted QC: 2007-11-05
• Study First Posted: 2007-11-06
• Primary Completion: 2010-10
• Study Completion: 2010-11
• Status Verified: 2011-02
• Last Update Submitted: 2011-02-22
• Last Update Posted: 2011-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
I5NP drug	I5NP (a small interfering RNA)	-
Placebo	placebo	-

Primary Outcome Measures

Name	Time	Method
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 4-8 patients per cohort	Reviewed at the conclusion of each cohort
Pharmacokinetics	Immediately following injection through 24 hrs

Trial Locations

Locations (11)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Virginia School of Medicine; 🇺🇸 Charlottesville, Virginia, United States

Tel Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Rabin Medical Center; 🇮🇱 Petah Tikva, Israel

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel

University Hospital of Geneva; 🇨🇭 Geneva, Switzerland

George Washington University; 🇺🇸 Washington, District of Columbia, United States

Lausanne University Hospital (CHUV); 🇨🇭 Lausanne, Switzerland

Texas Heart Institute at St. Luke's Episcopal Hospital; 🇺🇸 Houston, Texas, United States