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

Delayed Function of Renal Transplant Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02490202
• Other study ID #: SGTP-002
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 16, 2015
• Last updated: October 26, 2016
• Start date: August 2015
• Est. completion date: October 2016

Study information

• Verified date: October 2016
• Source: Prolong Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Delayed Function of Renal Transplant
• Delayed Graft Function

Intervention

Drug:
• SANGUINATE
Two (2) infusions of 320 mg/kg of SANGUINATE at Baseline and Day 1
• Normal Saline
Two (2) infusions of Normal Saline at an equal volume to SANGUINATE at Baseline and Day 1.

Locations

Country	Name	City	State
United States	Augusta University	Augusta	Georgia
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	UIC University of Illinois at Chicago	Chicago	Illinois
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Central Pennsylvania Transplant Foundation	Harrisburg	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	University of Pittsburg Medical Center	Pittsburgh	Pennsylvania
United States	California Institute of Renal Research	San Diego	California
United States	California Pacific Medical Center	San Francisco	California
United States	University of California San Francisco	San Francisco	California
United States	Tampa General Hospital	Tampa	Florida
United States	University of Toledo	Toledo	Ohio
United States	Medstar Georgetown University Hosiptal	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Prolong Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determination of sample size for Phase 3 based upon the results from Phase 2.		30 Days	No
Primary	Reduction of delayed graft function (DGF)	Reduction of delayed draft function will be measured by the number of dialysis sessions.	30 Days	No
Primary	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	Yes
Secondary	Proportion of subjects requiring dialysis for any reason in the first 7 days post-transplant		7 Days	Yes
Secondary	Proportion of subjects requiring dialysis only in the first 5 days post-transplant		5 Days	Yes
Secondary	Number of days of dialysis therapy.		30 Days	Yes
Secondary	Proportion of subjects with a fall in serum creatinine.		7 Days	Yes
Secondary	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	Yes
Secondary	Rate of change in estimated creatinine clearance and estimated glomerular filtration rate over time		Phase 2: 30 Days	Yes