I5NP is being developed for the prophylaxis of delayed graft function (DGF) in patients receiving renal transplants. The patient population of the current study will include patients undergoing deceased donor renal transplantation who are at risk for DGF. MedDRA version: 13.1 Level: LLT Classification code 10048747 Term: Renal graft function delayed System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: I5NP
Product Code: QPI-1002
Pharmaceutical Form: Injection
CAS Number: 1231737-88-4
Current Sponsor code: QPI-1002
Other descriptive name: I5NP
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Quark Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part B (the subject trial portion): 1. Patient is at least 18 years of age. 2. Patient has given informed consent. 3. Patient is willing to practice birth control. Female / Male 4. Women of childbearing potential test negative for pregnancy (either urine or serum) within 48 hours prior to transplant. 5. Patient is up-to-date on cancer screening according to site-specific guidelines and the past medical history is negative for biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ. 6. Patient is scheduled to receive kidney transplant from a deceased donor meeting the following criteria Part B exclusive: • Receipt of an ECD kidney that has been preserved by cold storage (ECD/CS) for the entire period of cold ischemia time (CIT)*, regardless of duration • Receipt of an ECD kidney that has been preserved by machine perfusion (ECD/MP**) for any interval of time during the period of cold ischemia, where total CIT* has been at least 26 hours • Receipt of an SCD kidney that has been preserved by cold storage (SCD/CS) where total CIT* has been at least 26 hours • Receipt of an SCD kidney that has been preserved by machine perfusion (SCD/MP**) for any interval of time during the period of cold ischemia, where total CIT* has been at least 26 hours. ________________________ * CIT will be estimated at screening based on the difference between the time of aortic cross-clamping in the donor and projected initiation of the arterial anastomotic procedure in the recipient) ** For purposes of this study, a “kidney that has been preserved by machine perfusion” means that the kidney has had any machine preservation (e.g. a kidney that was initially machine perfused but then removed from the pump and placed on cold storage, would be considered MP). 7. Patient is dialysis dependent at the time of transplant as documented by at least one of the following: • the requirement for at least 2 dialysis sessions/week during the 56 days prior to transplant, or • the planned removal of any remaining native kidney at the time of transplant, or • the investigator has provided documentation to the Medical Monitor that the patient has no remaining native renal function (e.g., documentation that the patient is anuric, with urine output =65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Patient has participated in an investigational drug study in the last 30 days. 2. Patient has known allergy or has participated in prior study with siRNA. 3. Patient is HCV-positive 4. Patient is HIV-positive 5. Patient is scheduled to undergo multiorgan transplantation. 6. Patient has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant). 7. Patient has planned transplant of kidneys from donors 1.5 mg/dL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part B portion: To determine the safety of I5NP when administered as a single intravenous push (IVP) to patients undergoing deceased donor kidney transplant. To assess the efficacy of I5NP in the prevention of delayed graft function (DGF) in patients at increased risk of DGF following deceased donor renal transplantation;Secondary Objective: To determine the dose(s) of I5NP to be studied in subsequent trials. To prospectively determine the feasibility and validity of additional efficacy endpoints in this study population. To inform the design of subsequent trials. ;Primary end point(s): The primary endpoint for Part B will be the incidence of DGF in the Intention-to-Treat (ITT) population of all randomized and transplanted patients, where DGF is defined as the need for acute dialysis within the first 7 days post-transplant excluding the following: • Dialysis performed during the first 24 hours for one or more of the following reasons: - Treatment of hyperkalemia or hypervolemia - Hyperacute rejection or other antibody-mediated acute rejection[1] - Technical vascular complications involving the allograft: renal arterial and/or venous thrombosis due to vascular injury or technical surgical complications. • Dialysis performed during the first 7 days post-transplant for one or more of the following reasons: - Obstructive uropathy[2] - Fulminant recurrence of primary disease (underlying etiology of ESRD)[1], including focal segmental glomerulosclerosis - A specific diagnosis of thrombotic microangiopathy (Thrombotic Thrombocytopenic Purpura or Hemolytic–Uremic Syndrome).[1] ___________________________________ [1] Biopsy-confirmed [2] Radiographically-confirmed ;Timepoint(s) of evaluation of this end point: 7 days post-transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Need for dialysis for any reason within 7 days post-transplant 2. Treatment difference in the need for dialysis within 7 days post-transplant for: a. Donor kidneys preserved using machine perfusion at any time pre-transplant b. Donor kidneys not preserved using machine perfusion at any time pre-transplant 3. Treatment difference in the absence of a decrease in the serum creatinine concentration of at least 10%/day for at least 3 consecutive days during the first week post-transplantation. 4. Treatment differences in the mean change from the pre-dose, post-reperfusion baseline serum creatinine and serum creatinine concentration at 24, 48, and 72 hours. 5. Treatment difference in the rate of change in renal function as determined from the slope of the plot of serum creatinine versus time at 6, 12, 24, 36, 48, 72, 96, and 120 hours post-transplant. 6. Treatment difference in the rate of change in renal function as determined from the slope of the plot of estimated GFR [eGFR - mL/min/1.73 m2, as determined from the (a) 4-variable MDRD equation and (b) Cockcroft-Gault equation after adjustment per 1.73 m2 body surface area versus time at 6, 12, 24, 36, 48, 72, 96, and 120 hours post-transplant. 7. Estimated GFR (standardized creatinine) as determined from the (a) 4-variable MDRD equation and (b) Cockcroft-Gault equation after adjustment per 1.73 m2 body surface area on days 1, 3, 7, 30, 90, and 180 post-transplant.;Timepoint(s) of evaluation of this end point: days 1, 3, 7, 30, 90, and 180 post-transplant | — |
Countries
Canada, Germany, Spain, United States
Contacts
Public ContactHarald von Eick (Managing Director)
CTI Clinical Trial and Consulting Services Europe GmbH
Outcome results
None listed