QPI-1002 is being developed for the prevention of Delayed Graft Function 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: 18.1 Level: PT Classification code 10076664 Term: Delayed graft function System Organ Class: 10022117 - Injury, poisoning and procedural complications
Conditions
Interventions
Product Name: I5NP
Product Code: QPI-1002
Pharmaceutical Form: Injection
INN or Proposed INN: Not applied
CAS Number: 1231737-88-4
Current Sponsor code: QPI-1002
Other descriptive name: I5NP
Concentra
Sponsors
Quark Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has the ability to understand the requirements of the study, is able to provide written informed consent (including consent for the use and disclosure of research related health information) and is willing and able to comply with the requirements of the study protocol (including required study visits). 2. Male or female at least 18 years of age. 3. Has dialysis dependent renal failure initiated at least 2 months prior to transplantation. 4. Is to be a recipient of a transplant from a deceased donor (brain death criteria) ? 45 years of age. 5. Based on donor age, the following requirements for the risk of DGF (determined using the Irish DGF risk assessment nomogram) and cold ischemia time (CIT) must be met: a. Donor age 45 ? 59 years: estimated DGF risk >= 20% and estimated CIT >= 16 hour b. Donor age >= 60 years: no minimum estimated DGF risk or minimum estimated CIT 6. Is able to comply with the requirement of antibody induction therapy with rabbit polyclonal anti-thymocyte globulin or anti-CD25 (anti-IL2R) monoclonal antibodies per center standard of care. 7. A female subject is eligible to enter the study if she is: a. Not pregnant or nursing b. Of non-childbearing potential (i.e., post-menopausal defined as having been amenorrheic for at least 1 year prior to screening, or has had a bilateral tubal ligation at least 6 months prior to administration of study drug or bilateral oophorectomy or complete hysterectomy). c. If of childbearing potential, must have a negative serum pregnancy test within 48 hours prior to transplant surgery and be using an effective means of contraception (per the site-specific guidelines or using 2 methods of birth control concurrently, whichever is more stringent) which will be continued until the Day 180 visit. 8. Male subjects with female partners of childbearing potential must agree to use an effective means of contraception (per the site-specific guidelines or use 2 methods of birth control concurrently, whichever is more stringent), which will be continued until the Day 180 visit. 9. Must be up-to-date on cancer screening according to site-specific guidelines and past medical history must be negative for biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ or carcinoma of the cervix in situ. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 507 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 127
Exclusion criteria
Exclusion criteria: 1. Recipient of a live donor kidney or a kidney from a donation after cardiac death (DCD) donor. 2. Recipient of donor kidney preserved with normothermic machine perfusion. 3. Scheduled to undergo multiorgan transplantation. 4. Has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant). 5. Has planned transplant of dual kidneys (from the same donor) transplanted not en bloc. 6. Has lost first kidney transplant due to graft thrombosis. 7. Is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy under another IND/CTA for ischemic/reperfusion injury immediately prior to organ recovery. 1. Recipient of a live donor kidney or a kidney from a donation after cardiac death (DCD) donor. 2. Recipient of donor kidney preserved with normothermic machine perfusion. 3. Scheduled to undergo multiorgan transplantation. 4. Has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant). 5. Has planned transplant of dual kidneys (from the same donor) transplanted not en bloc. 6. Has lost first kidney transplant due to graft thrombosis. 7. Is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy under another IND/CTA for ischemic/reperfusion injury immediately prior to organ recovery. 8. Is scheduled to receive an ABO-incompatible donor kidney. 9. Has a positive T- or B-cell cross-match by NIH anti-globulin lymphocytotoxicity method or CDC cross-match method, if performed. 10. Has a positive T- or B-cell flow cross-match AND donor specific anti-HLA antibody (DSA) detected by flow cytometry, Luminex® based antigen-specific anti-HLA antibody testing, or by similar methodology, if performed. 11. Has undergone desensitization to remove donor specific anti-HLA antibodies prior to transplantation. 12. Has participated in an investigational study within the last 30 days or received an investigational product within 5 half-lives of the study drug administration, whichever is longest. 13. Has known allergy to or has participated in a prior study with siRNA. 14. Has a history of HBV (Note: subjects with a serological profile suggestive of clearance, or prior antiviral treatment of a prior HBV infection, may be enrolled with the approval of the Medical Monitor). 15. Has a history of HIV. 16. Recipient of a known HIV positive donor kidney. 17. Is HCV-positive (detectable HCV RNA) (Note: Subjects at least 24 weeks from completion of treatment with an approved antiviral regimen and who remain free of HCV as determined by HCV RNA testing may be enrolled. Subjects who have been cleared of HCV virus after treatment with an unapproved regimen should be approved by the Medical Monitor). 18. Has history or presence of a medical condition or disease or psychiatric condition that in the investigator's assessment would place the patient at an unacceptable risk for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine the efficacy of QPI-1002 to reduce the incidence and severity of delayed graft function in comparison to placebo in recipients of a donation after brain death (DBD) older donor kidney. 2. To assess the safety and tolerability of QPI-1002 in comparison to placebo when administered to recipients of a DBD donor kidney.;Secondary Objective: Not applicable;Primary end point(s): 1. The primary endpoint for the study is delayed graft function (DGF) , defined as the as the number of dialysis sessions through Day 30 for subjects who started dialysis beginning in the first 7 days post-transplant. a. Dialysis sessions will be counted through Day 30 post-transplant, or until a 7 day dialysis free period occurs, whichever occurs first. Individual hemo- or peritoneal dialysis sessions will be counted individually. Subjects who receive continuous peritoneal filtration will count as 3 sessions/week. Continuous hemofiltration will also be counted as 3 sessions/week. b. A subject who does not have DGF (i.e., dialysis in the first 7 days post-transplant) will be classified as having 0 dialysis sessions. c. Subjects who drop out on or before Day 7, regardless of the reason for dropout (e.g., experience primary non-function (PNF), graft loss, death or lost-to-follow up), will be considered to have failed the primary endpoint and will be assigned the maximum number of dialysis sessions from the day of dropout. Dialysis session is defined in the protocol. The maximum number of dialysis sessions will be the observed number of dialysis sessions (to the point of drop out or loss) plus 3 dialysis sessions per week from that point to Day 30. This reflects the typical practice of administration of 3 dialysis sessions per week inclusive of the actual number of dialysis sessions observed. PNF is defined for efficacy analysis as continuous requirement for dialysis starting in the first 7 days after transplant and lasting for at least 60 days pos | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant. 2. The proportion of subjects with a fall in serum creatinine of ? 10% on three consecutive days in the first 7 days post-transplant.;Timepoint(s) of evaluation of this end point: 7 days post-transplant | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Operations
Quark Pharmaceuticals, Inc.
Outcome results
None listed