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

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

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.

Study Overview

• Status: Completed
• Conditions: Delayed Function of Renal Transplant
• Intervention / Treatment: Drug: SANGUINATE; Drug: Normal Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • California
    • Los Angeles, California, United States, 90024
      • University of California, Los Angeles
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Medstar Georgetown University Hosiptal
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • UIC University of Illinois at Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48212
      • Henry Ford Hospital
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Saint Barnabas Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
    • Toledo, Ohio, United States, 43537
      • University of Toledo
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17104
      • Central Pennsylvania Transplant Foundation
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburg Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SANGUINATE; Two (2) infusions of SANGUINATE	Drug: SANGUINATE; Two (2) infusions of 320 mg/kg of SANGUINATE at Baseline and Day 1; Other Names: pegylated carboxyhemoglobin bovine
Placebo Comparator: Normal Saline; Two (2) infusions of Normal Saline	Drug: Normal Saline; Two (2) infusions of Normal Saline at an equal volume to SANGUINATE at Baseline and Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of delayed graft function (DGF)	Reduction of delayed draft function will be measured by the number of dialysis sessions.	30 Days
Participants With at Least One Occurrence of Safety Composite Endpoint by Treatment Group	Composite endpoint defined by changes in vital signs, electrocardiographic, biochemical, hematological, and urinalysis, graft loss, death and other reported adverse events	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 Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Determination of sample size for Phase 3 based upon the results from Phase 2.	30 Days

Collaborators and Investigators

• Sponsor: Prolong Pharmaceuticals
• Investigators: Study Director: Hemant Misra, PhD, Prolong Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 16, 2015
• First Submitted That Met QC Criteria: July 1, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Estimate): October 27, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function
• Other Study ID Numbers: SGTP-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO