Acute Renal FailurePhase 1NCT00683553
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)
A Phase 1 study testing I5NP in people with Acute Renal Failure and Acute Kidney Injury, run by Quark Pharmaceuticals at 10 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 85 years
- Conditions the study is for
- Acute Renal Failure, Acute Kidney Injury
- What is being tested?
- I5NP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 10 sitesUnited States
- Study dates
- May 2008to Sep 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 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.
- 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 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.
Show all 19Show 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]
- 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
- 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
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
University of Virginia School of Medicine
Charlottesville, Virginia, 22908-0688
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Texas Heart Institute
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
University of Texas
Houston, Texas, 77030
Mayo Clinic Hospital
Phoenix, Arizona, 85054
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Washington University
St Louis, Missouri, 63110
George Washington University
Washington D.C., District of Columbia, 20037
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 at High Risk of Acute Kidney Injury 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 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.
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 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
- Acute Renal Failure, Acute Kidney Injury
- Being tested
- I5NP, Placebo
- Keywords
- Acute Renal Failure, Acute Kidney Injury
- 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.
I5NPDrug
Also called QPI-1002
Single IV injection of experimental drug given in escalated doses at 0.5, 1.5, 5.0 and 10 mg/kg doses to different patients
PlaceboDrug
Single IV injection of saline
| Study group | Role | What they receive |
|---|---|---|
| I5NP drug | Experimental | Not described Receives: Drug: I5NP |
| Placebo | Placebo comparator | Not described Receives: Drug: I5NP; 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 6-12 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 posted23 May 2008 (estimated)
- Study startMay 2008
- Primary completionMay 2010
- Study completionSep 2010
Why it stopped: Lack of an available patient population
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Renal FailureStudies 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
- 3 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
- NCT00683553
- Sponsor's protocol ID
- QRK.004
- Status last verified
- Nov 2010
- First submitted
- 21 May 2008
- Last updated
- 16 Nov 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2010. 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 at High Risk of Acute Kidney Injury Undergoing Major Cardiovascular Surgery
- ClinicalTrials.gov ID
- NCT00683553
- Acronym / sponsor ID
- QRK.004
- Conditions
- Acute Renal Failure, Acute Kidney Injury
- Keywords
- Acute Renal Failure, Acute Kidney Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of an available patient population
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Quark PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- May 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 23 May 2008 (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 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.
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 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 |
| Placebo | Placebo comparator | Drug: I5NP, 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 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
Key exclusion criteria (19 listed)
- Patient has had cancer or may be predisposed due to a family history of:
- 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.
- Patient has participated in a study of an experimental therapy in the last 30 days
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 |
|---|---|---|
| I5NPAlso: QPI-1002Single IV injection of experimental drug given in escalated doses at 0.5, 1.5, 5.0 and 10 mg/kg doses to different patients | Drug | I5NP drug, Placebo |
| PlaceboSingle IV injection of saline | Drug | Placebo |
Primary outcome
Number of Dose Limiting Toxicities (DLTs) observed among 4 cohorts of 6-12 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 was stopped early (reason given: Lack of an available patient population). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2010.
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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
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing I5NP in people with Acute Renal Failure and Acute Kidney Injury, run by Quark Pharmaceuticals at 10 sites in United States.
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 19 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: stopped early, as of the sponsor's last update on 16 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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 was stopped early (reason given: Lack of an available patient population). Results are not available in the source record.
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 6-12 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 16 Nov 2010.