Injury of KidneyPhase 1NCT00554359
A Dose Escalation and Safety Study of I5NP in Patients Undergoing Major Cardiovascular Surgery
A Phase 1 study testing I5NP (a small interfering RNA) in people with Injury of Kidney and Acute Renal Failure, run by Quark Pharmaceuticals at 11 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Injury of Kidney, Acute Renal Failure
- What is being tested?
- I5NP (a small interfering RNA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Aug 2007to Nov 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 32Show fewer
- 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)
- 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
- Baseline serum creatinine > 3.0 mg/dL and/or an estimated GFR of < 30 mL/min/1.73 m2, as calculated by the Modification of Diet in Renal Disease [MDRD] Study equation: eGFR (mL/min/1.73 m2) = [186 x (SCr)] - [1.154 x (Age)] - [0.203 x (0.742 if female or 1.210 if African-American female)] where SCr: serum creatinine in mg/dL and age is in years
- 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 < 48 hours prior to surgery
- In the opinion of the investigator a pre-operative concomitant disease or clinical finding such as an abnormality in clinical lab results, chest X-ray, EKG, or physical examination finding that significantly raises the risk of perioperative complications precludes dosing of the patient
- Patient on CBM for > 3 hours
- Patient experienced major blood loss (>15 units)
- Use of balloon pump or other LVAD during surgery;
- In the opinion of the investigator, an intra-operative complication precludes dosing of the patient
- Cardiac Index < 2.1 L/min/m2 (applies only to patients with a Swan-Ganz or other PA catheter)
- Patient has a body temperature ≥ 40 °C
- Use of IABP post-surgery
- Fluid imbalance in excess of 15 liters
- PaO2:FiO2 < 250
- Patient receiving ≥ 3 concurrent vasopressors to maintain hemodynamic stability
- In the opinion of the investigator a post-operative complication precludes dosing of the patient
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States6 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Virginia School of Medicine
Charlottesville, Virginia, 22908-0688
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Texas Heart Institute at St. Luke's Episcopal Hospital
Houston, Texas, 77030
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
George Washington University
Washington D.C., District of Columbia, 20037
Israel3 sites
Shaare Zedek Medical Center
Jerusalem, 91031
Rabin Medical Center
Petah Tikva, 49100
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
Switzerland2 sites
University Hospital of Geneva
Geneva
Lausanne University Hospital (CHUV)
Lausanne, CH-1011
About this study
Official title: A Phase I, Randomized, Double-Blind, Dose Escalation Trial of the Safety and Pharmacokinetics of a Single Intravenous Injection of I5NP in Patients Undergoing Major Cardiovascular Surgery
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.
Read the 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.
- Conditions
- Injury of Kidney, Acute Renal Failure
- Being tested
- I5NP (a small interfering RNA), placebo
- Keywords
- Acute Kidney Injury, Acute Renal Failure
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
I5NP (a small interfering RNA)Drug
Single IV injection of experimental drug
placeboDrug
Single IV injection of saline
| Study group | Role | What they receive |
|---|---|---|
| I5NP drug | Experimental | Not described Receives: Drug: I5NP (a small interfering RNA) |
| Placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 4-8 patients per cohort
Measured: Reviewed at the conclusion of each cohort
Pharmacokinetics
Measured: Immediately following injection through 24 hrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2007 (estimated)
- Study startAug 2007
- Primary completionOct 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Injury of KidneyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Quark Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Martin S. Polinsky, M.D., Study director, Quark Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00554359
- Sponsor's protocol ID
- QRK.002
- Status last verified
- Feb 2011
- First submitted
- 4 Nov 2007
- Last updated
- 23 Feb 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-Blind, Dose Escalation Trial of the Safety and Pharmacokinetics of a Single Intravenous Injection of I5NP in Patients Undergoing Major Cardiovascular Surgery
- ClinicalTrials.gov ID
- NCT00554359
- Acronym / sponsor ID
- QRK.002
- Conditions
- Injury of Kidney, Acute Renal Failure
- Keywords
- Acute Kidney Injury, Acute Renal Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Quark PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Oct 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 6 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| I5NP drug | Experimental | Drug: I5NP (a small interfering RNA) |
| Placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (32 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| I5NP (a small interfering RNA)Single IV injection of experimental drug | Drug | I5NP drug |
| placeboSingle IV injection of saline | Drug | Placebo |
Primary outcome
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 4-8 patients per cohort
Time frame: Reviewed at the conclusion of each cohort
Pharmacokinetics
Time frame: Immediately following injection through 24 hrs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin S. Polinsky, M.D. study director
Quark Pharmaceuticals
11 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing I5NP (a small interfering RNA) in people with Injury of Kidney and Acute Renal Failure, run by Quark Pharmaceuticals at 11 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Israel, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 4-8 patients per cohort (time frame: Reviewed at the conclusion of each cohort). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2011.