Study to Improve Renal Function After Kidney Transplantation

Delayed Graft Function Clinical Trial

Official title:

Multicenter Pilot Study of BB3 to Improve Renal Function in Patients With Signs and Symptoms of Significant Renal Injury After Kidney Transplantation and at Risk for Dialysis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01286727
• Other study ID #: 001-09
• Secondary ID: 2R44DK066654
• Status: Active, not recruiting
• Phase: Phase 2
• First received: January 27, 2011
• Last updated: May 4, 2015
• Start date: February 2010
• Est. completion date: February 2016

Study information

• Verified date: October 2014
• Source: Angion Biomedica Corp
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to evaluate the safety and activity of a investigational drug in improving renal function in patients who have undergone renal transplantation and have signs and symptoms of significant renal injury and are at risk for dialysis.

Description:

Delayed graft function (DGF) is generally defined as the need for dialysis during the first 7 days after transplantation although the definition can also include failure to improve preexisting renal function. DGF is an important problem in renal allograft transplantation that affects approximately 25% of transplanted cadaveric kidneys. It has generally been observed that delayed graft function has been associated with reduced graft survival. In addition to an association of DGF with graft loss, DGF imposes an economic burden due to prolonged hospitalization and dialysis. The strongest association with occurrence of DGF is ischemia around the time of transplantation. Aside from approaches to minimize ischemia time and use of antibody induction, there are no good specific therapeutic options to prevent or treat delayed graft function. This study is designed to evaluate the safety and activity of an investigational drug in improving renal function in patients who have undergone renal transplantation and have signs and symptoms of significant renal injury and are at risk for dialysis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: February 2016
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males and females = 18 years of age

2. Had renal transplantation due to end stage disease requiring chronic dialysis

3. Study drug can be administered within 36 hours after transplantation

4. Received kidney from healthy donor or donor with history of diabetes mellitus or hypertension

5. Donor terminal serum creatinine = 2.2 mg/dL.

6. No urine output, OR average urine output of < 50 cc/H over 8 or more consecutive hours, OR normal urine output following transplantation that diminished to average of < 50 cc/H over 8 or more consecutive hours, OR creatinine reduction ratio at 24 hours after transplantation to pre-transplantation is < 30%.

7. Reason for low urine output is unlikely due to structural changes. If clinically indicated, an ultrasound will be performed

8. Dry weight to< 120kg and BMI <35

9. Women of child bearing potential have a negative serum pregnancy test prior to transplantation.

10. Women of child bearing potential (including perimenopausal women who have had a menstrual period within 1 year) must agree to use 2 forms of effective birth control regimen (at least one-barrier method) during the 28-day study period. Men must agree to use condoms during the 28-day study period.

11. In the opinion of the investigator, the subject is capable of understanding and complying with the protocol.

12. Subjects must have signed the informed consent document prior to performance of any study related procedure including screening procedure.

Exclusion Criteria:

1. Subject with normal urine output and not requiring dialysis prior to renal transplantation (i.e., had pre-emptive renal transplantation).

2. Signs and symptoms of volume depletion.

3. Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.

4. Recipient of pediatric en-bloc kidney transplantation.

5. Recipient of kidney with cold ischemia time > 40 hours

6. Has measurable donor-specific antibody or positive cross-match requiring deviation from standard immunosuppressive therapy.

7. Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment into this study.

8. Concurrent sepsis or active bacterial infection.

9. Have an active malignancy or history of solid, metastatic or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed.

10. Women of child bearing potential who are breast feeding.

11. History of positive HIV test.

12. History of rheumatoid arthritis.

13. Subjects who require the cytochrome P450 1A2 (CYP1A2) inhibitors, ciprofloxacin and/or fluvoxamine (Luvox®)

14. Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.

15. Subject is not deemed medically stable for the study in the opinion of the Investigator or the subject's primary nephrologist.

Study Design

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

Related Conditions & MeSH terms

• Delayed Graft Function

Intervention

Drug:
• BB3
intravenous drug

Locations

Country	Name	City	State
United States	Division of Transplant Surgery, University of Maryland School of Medicine, University of Maryland Medical Center	Baltimore	Maryland
United States	State University of New York at Buffalo	Buffalo	New York
United States	The Methodist Hospital	Houston	Texas
United States	California Institute of Renal Research	San Diego	California
United States	Medstar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Angion Biomedica Corp	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine production	mean time (days) until production of = 50 cc/H of urine over a 12 hour period	28 days	No
Secondary	Change from baseline urine production	Change from baseline urine production (cc/H) at each of the following time points: Day 3, Day 7, Day 14, and Day 28	28 days	No
Secondary	creatinine clearance	Mean measured 24-hour creatinine clearance at Days 3, 7, 14, and 28	28 days	No
Secondary	Incidence of delayed graft function	Incidence of delayed graft function (required dialysis due to inadequate renal function during the 7 days after transplantation)	7 days	No
Secondary	Number of dialysis sessions	Number of dialysis sessions through Day 7, 14, and 28	28 days	No
Secondary	Daily urine output	Mean total daily urine output through Day 14	14 days	No
Secondary	Mean serum creatinine	Mean serum creatinine at Days 4, 7, 10, 14, and 28	28 days	No
Secondary	Number of acute rejection episodes	Number of acute rejection episodes	28 days	No
Secondary	Length of hospitalization following transplantation	Length of hospitalization following transplantation	28 days	No
Secondary	Biomarkers	Comparison of biomarkers	28 days	No
Secondary	adverse events, clinical laboratory evaluations, vital signs, ECG results	Safety assessments include adverse events, clinical laboratory evaluations, vital signs, ECG results.	28 days	Yes