Study to Improve Renal Function After Kidney Transplantation

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

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.

Study Overview

• Status: Unknown
• Conditions: Delayed Graft Function
• Intervention / Treatment: Drug: BB3

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • California Institute of Renal Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Division of Transplant Surgery, University of Maryland School of Medicine, University of Maryland Medical Center
  • New York
    • Buffalo, New York, United States, 14215
      • State University of New York at Buffalo
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital

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. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Normal Saline; Placebo
Active Comparator: BB3	Drug: BB3; intravenous drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine production	mean time (days) until production of ≥ 50 cc/H of urine over a 12 hour period	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
creatinine clearance	Mean measured 24-hour creatinine clearance at Days 3, 7, 14, and 28	28 days
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
Number of dialysis sessions	Number of dialysis sessions through Day 7, 14, and 28	28 days
Daily urine output	Mean total daily urine output through Day 14	14 days
Mean serum creatinine	Mean serum creatinine at Days 4, 7, 10, 14, and 28	28 days
Number of acute rejection episodes	Number of acute rejection episodes	28 days
Length of hospitalization following transplantation	Length of hospitalization following transplantation	28 days
Biomarkers	Comparison of biomarkers	28 days
adverse events, clinical laboratory evaluations, vital signs, ECG results	Safety assessments include adverse events, clinical laboratory evaluations, vital signs, ECG results.	28 days

Collaborators and Investigators

• Sponsor: Angion Biomedica Corp
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Study Director: Weizhong Cai, PhD, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): January 1, 2015
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: January 27, 2011
• First Submitted That Met QC Criteria: January 28, 2011
• First Posted (Estimate): January 31, 2011

Study Record Updates

• Last Update Posted (Estimate): May 5, 2015
• Last Update Submitted That Met QC Criteria: May 4, 2015
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function
• Other Study ID Numbers: 001-09; 2R44DK066654 (U.S. NIH Grant/Contract)