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Efficacy and Safety of SANGUINATE™ for Reduction of Delayed Graft Function in Patients Receiving a Kidney Transplant

Phase 2
Completed
Conditions
Delayed Function of Renal Transplant
Interventions
Drug: Normal Saline
Registration Number
NCT02490202
Lead Sponsor
Prolong Pharmaceuticals
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
60
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SANGUINATESANGUINATETwo (2) infusions of SANGUINATE
Normal SalineNormal SalineTwo (2) infusions of Normal Saline
Primary Outcome Measures
NameTimeMethod
Reduction of delayed graft function (DGF)30 Days

Reduction of delayed draft function will be measured by the number of dialysis sessions.

Participants With at Least One Occurrence of Safety Composite Endpoint by Treatment GroupPhase 2 - 30 Days; Phase 3: Safety - 90 days; Serious Adverse Events and Adverse Events of Special Interest - 180 Days; Graft Survival - 365 Days

Composite endpoint defined by changes in vital signs, electrocardiographic, biochemical, hematological, and urinalysis, graft loss, death and other reported adverse events

Secondary Outcome Measures
NameTimeMethod
Proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant7 Days
Proportion of subjects requiring dialysis only in the first 5 days post-transplant5 Days
Number of days of dialysis therapy.30 Days
Proportion of subjects with a fall in serum creatinine.7 Days
Rate of change in estimated creatinine clearance and estimated glomerular filtration rate over timePhase 2: 30 Days
Proportion of subjects with a serum creatinine greater than 3 mg/dL, but who did not require dialysis by Day 5 post-transplant5 Days

Trial Locations

Locations (20)

University of California, Los Angeles

🇺🇸

Los Angeles, California, United States

University of Pittsburg Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Mayo Clinic Phoenix

🇺🇸

Phoenix, Arizona, United States

California Institute of Renal Research

🇺🇸

San Diego, California, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

California Pacific Medical Center

🇺🇸

San Francisco, California, United States

Medstar Georgetown University Hosiptal

🇺🇸

Washington, District of Columbia, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

UIC University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Augusta University

🇺🇸

Augusta, Georgia, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

The Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Saint Barnabas Medical Center

🇺🇸

Livingston, New Jersey, United States

University of Toledo

🇺🇸

Toledo, Ohio, United States

Central Pennsylvania Transplant Foundation

🇺🇸

Harrisburg, Pennsylvania, United States

University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Ochsner Medical Center

🇺🇸

New Orleans, Louisiana, United States

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

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