Clinical trial NCT02490202: Efficacy and Safety of SANGUINATE™ for Reduction of Delayed Graft Function in Patients Receiving a Kidney Transplant
Official title: A Randomized, Placebo-controlled, Prospective, Double-blind, Multicenter Phase 2/3 Study of the Efficacy and Safety of SANGUINATE™ for Reduction of Delayed Graft Function in Recipients of a Donation After Brain Death Kidney Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Delayed Function of Renal Transplant
Lead sponsor: Prolong Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-07-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Safety and efficacy study of SANGUINATE on reduction of delayed graft function (DGF) in patients who will be recipients of a donation after brain death (DBD) donor kidney.

Detailed description: Phase 2: Sixty (60) adult subjects who will be recipients of a donation after brain death (DBD) donor kidney and who meet all eligibility criteria will be randomized 1:1 within 48 hours prior to transplant surgery to receive: two infusions of SANGUINATE at a dose of 320 mg/kg or placebo on the day of surgery and approximately 24 hours after surgery. Patients will be hospitalized for up to 5 days and the study duration will be 30 days. Results will be used to inform the study design characteristics for Phase III, including sample size.

Phase III: The same inclusion/exclusion requirements, dosing schedule, hospitalization stay and outpatient visits as in Phase II with additional visits scheduled at Day 90, Day 180 and Day 365. Study duration will be 365 days.

Eligibility criteria: Inclusion Criteria:

1. Able to understand and provide written informed consent.
2. Male or female subject at least 18 years of age.
3. Dialysis-dependent renal failure initiated at least 3 months prior to transplantation.
4. Subject is to be the recipient of a first kidney transplant from a deceased donor (brain death criteria).
5. Is able to receive intravenous infusions of study drug.
6. Anticipated donor organ cold ischemia time \< 30 hours.
7. A calculated prediction of DGF risk of least 25%.
8. Females of childbearing potential must agree to use 2 forms of effective birth control regimen (at least one-barrier method) during the initial 30-day study period.
9. Male subjects must agree to use condoms or other suitable means of pregnancy prevention.

Exclusion Criteria:

1. Has received a blood transfusion of packed red blood cells (PRBC), other than with leukocyte-poor blood, within the 90-day period prior to screening.
2. Recipient of a live donor kidney or a kidney from a donation after cardiac death (DCD) donor.
3. Recipient of donor kidney preserved with normothermic machine perfusion.
4. Is scheduled to undergo multi-organ transplantation.
5. Has planned transplant of kidney(s) from a donor \< 6 years of age.
6. Has planned transplant of kidneys that are implanted en bloc (dual kidney transplant).
7. Has planned transplant of dual kidneys (from the same donor) transplanted not en bloc.
8. Body Mass Index (BMI) \> 38 kg/m2
9. Is scheduled for transplantation of a kidney from a donor who is known to have received an investigational therapy (under another Investigational New Drug) for ischemic/reperfusion injury immediately prior to organ recovery.
10. Is scheduled to receive an blood type-incompatible donor kidney.
11. Has undergone desensitization to remove antibodies prior to transplantation.
12. Total bilirubin \> 1.5 mg per dL, transaminase more than twice the upper limit of normal or evidence of hepatic insufficiency
13. 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. Potential subjects participating in a strictly observational study or a study involving approved treatments should be discussed with the Medical Monitor.
14. Has a history of human immunodeficiency virus (HIV)
15. History or presence of active substance abuse (illicit drugs or alcohol) in the previous 6 months, as believed by the Investigator
16. Presence of ECG-based evidence of acute myocardial infarction, unstable angina, decompensated heart failure, third degree heart block or cardiac arrhythmia associated with hemodynamic instability
17. History or presence of any disease or psychiatric condition that in the Investigator's assessment that would increase the risk to subjects associated with study participation, drug administration or interpretation of results
18. History of biopsy-confirmed malignancy within 5 years of randomization, with the exception of adequately treated basal cell or squamous cell carcinoma in situ skin lesions, carcinoma of the cervix in situ, or early detected prostate cancer.
19. Female subject who is pregnant or breast feeding.

Primary outcomes:
measure: Reduction of delayed graft function (DGF)
timeFrame: 30 Days
measure: Participants With at Least One Occurrence of Safety Composite Endpoint by Treatment Group
timeFrame: Phase 2 - 30 Days; Phase 3: Safety - 90 days; Serious Adverse Events and Adverse Events of Special Interest - 180 Days; Graft Survival - 365 Days
Secondary outcomes:
measure: Proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant
timeFrame: 7 Days
measure: Proportion of subjects requiring dialysis only in the first 5 days post-transplant
timeFrame: 5 Days
measure: Number of days of dialysis therapy.
timeFrame: 30 Days
measure: Proportion of subjects with a fall in serum creatinine.
timeFrame: 7 Days
measure: Proportion of subjects with a serum creatinine greater than 3 mg/dL, but who did not require dialysis by Day 5 post-transplant
timeFrame: 5 Days
measure: Rate of change in estimated creatinine clearance and estimated glomerular filtration rate over time
timeFrame: Phase 2: 30 Days
Other outcomes:
measure: Determination of sample size for Phase 3 based upon the results from Phase 2.
timeFrame: 30 Days
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Diego
country: United States
facility: California Institute of Renal Research
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Washington
country: United States
facility: Medstar Georgetown University Hosiptal
state: District of Columbia
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: UIC University of Illinois at Chicago
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Medical Center
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Harrisburg
country: United States
facility: Central Pennsylvania Transplant Foundation
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Prolong Pharmaceuticals
name: Hemant Misra, PhD
role: STUDY_DIRECTOR
References: