QPI-1002 for Prevention of Delayed Graft Function in Recipients of an Older Donor Kidney Transplant

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the reduction in incidence and severity of delayed graft function with kidney allografts from donors >45 years after brain death (DBD).

Detailed Description
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This is a Phase 3 randomized, placebo-controlled, double-blind, multi-center trial stratified by donor age and by region to evaluate the reduction in incidence and severity of delayed graft function with kidney allografts from DBD donors who were at least 45 years of age.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of QPI-1002 for Prevention of Delayed Graft Function in Recipients of a Donation After Brain Death Older Donor Kidney Transplant

Conditions
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Delayed Graft Function

Intervention / Treatment
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* Drug: QPI-1002
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has the ability to understand the requirements of the study, is able to provide written informed consent and is willing and able to comply with the requirements of the study protocol. Male or female at least 18 years of age. Has dialysis dependent renal failure initiated at least 2 months prior to transplantation. Is to be a recipient of a transplant from a deceased donor (brain death criteria) ≥ 45 years of age. 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: Donor age 45 - 59 years: estimated DGF risk ≥ 20% and estimated CIT ≥ 10 hour Donor age ≥ 60 years: no minimum estimated DGF risk or minimum estimated CIT 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. 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. Exclusion Criteria: Recipient of a live donor kidney or a kidney from a donation after cardiac death (DCD) donor. Recipient of donor kidney preserved with normothermic machine perfusion. Scheduled to undergo multiorgan transplantation. Has a planned transplant of kidneys that are implanted en bloc (dual kidney transplant). Has planned transplant of dual kidneys (from the same donor) transplanted not en bloc. Has lost first kidney transplant due to graft thrombosis. 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. Is scheduled to receive an ABO-incompatible donor kidney. Has a positive T- or B-cell cross-match by NIH anti-globulin lymphocytotoxicity method or CDC crossmatch method, if performed. 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. Has undergone desensitization to remove donor specific anti-HLA antibodies prior to transplantation. 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. Has known allergy to or has participated in a prior study with siRNA. 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). Has a history of HIV. Recipient of a known HIV positive donor kidney. 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: QPI-1002<br>QPI-1002 Injection, single dose | Drug: QPI-1002<br>* IV injection<br>|
| Placebo Comparator: Placebo<br>isotonic saline | Other: Placebo<br>* isotonic saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of dialysis sessions through Day 30 for subjects who started dialysis beginning in the first 7 days post-transplant. |  | Day 0 to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant. |  | Day 0 to Day 7 | 
| The proportion of subjects with a decrease in serum creatinine of ≥ 10% on three consecutive days in the first 7 days post-transplant. |  | Day 0 to Day 7 |