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

NCT00554359 | Completed Phase 1 DMC

• 1 other identifier: QRK.002
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 11

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.

Conditions

Injury of Kidney; Acute Renal Failure

Keywords

Acute Kidney Injury; Acute Renal Failure

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

I5NP drug

EXPERIMENTAL

Drug: I5NP (a small interfering RNA)

Placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

I5NP (a small interfering RNA) DRUG

Single IV injection of experimental drug

I5NP drug

placebo DRUG

Single IV injection of saline

Placebo

Eligibility Criteria

• Age: 21 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 non-emergent coronary artery bypass graft (CABG) and/or valve replacement surgery
• Patient has a cumulative score of 0 to 8 on the Cleveland Clinic Foundation (CCF) Acute Kidney Injury (AKI) risk factor scale
• 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.
• Patient must have been on cardiopulmonary bypass machine (CBM)
• Patient must be in the ICU for dosing to facilitate study procedures including PK blood draws and PK urine sampling

You may not qualify if:

• Patient has undergone any organ transplant
• Patient who has had cancer or may be predisposed to develop cancers such as those with family history of cancers in multiple relatives {i.e., Familial Polyposis Coli, those with family history of Von Hippel Landau disease (associated with renal cell cancers and renal cysts) and those with family history of Li-Fraumeni syndrome (associated with inherited mutations of the p53 tumor-suppressor gene)}
• 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
• Patient has an underlying medical condition which increases the risk of perioperative complications, such as poorly controlled diabetes mellitus or hypertension or significant chronic obstructive pulmonary disease (COPD)
• 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 \[this criterion does NOT apply to topical steroids and inhalation steroids for chronic obstructive pulmonary disease (COPD) and/or asthma\]
• Patient requires pre-operative dialysis or is currently on dialysis
• Patient is undergoing aortic aneurism repair
• Pre-operative extracorporeal membrane oxygenation
• Pre-operative tracheotomy, or mechanical ventilation
• Patient has Intra-Arterial Balloon Pump (IABP) or other Left Ventricular Assist Device (LVAD)

Sponsors & Collaborators

• Quark Pharmaceuticals: lead

Study Sites (11)

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Texas Heart Institute at St. Luke's Episcopal Hospital

Houston, Texas, 77030, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22908-0688, United States

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

University Hospital of Geneva

Geneva, Switzerland

Location

Lausanne University Hospital (CHUV)

Lausanne, CH-1011, Switzerland

Location

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Martin S. Polinsky, M.D.

  Quark Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 4, 2007
• First Posted: November 6, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2010
• Last Updated: February 23, 2011

Record last verified: 2011-02

Locations

US (6); CH (2); IL (3)