Study on Delayed Graft Function Using Paired Kidneys

Pilot Study of BB3 to Improve Renal Function in Patients With Signs and Symptoms of Significant Renal Injury After Kidney Transplantation From Donors After Cardiac Death

The study is designed to evaluate the safety and efficacy of an intravenously administered drug in recipients of kidneys from cardiac death donors who are risk for developing delayed graft function.

Study Overview

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

Detailed Description

Renal transplantation is the most effective and cost-efficient form of renal replacement therapy for a burgeoning population that presents with end-stage renal disease. Although organ donation has become a national priority, the gap between the number of patients awaiting a kidney versus the number of available kidneys continues to widen exponentially. In many countries within the European Union, utilization of "donation after cardiac death" (DCD) kidneys is steadily increasing, expanding the donor pool by > 50%. Given the high incidence of cardiac deaths in the US, aggressive pursuit of the DCD kidney pool could potentially reduce waitlist periods to months, if not days. Risk for delayed graft function (DGF) with the attendant risks for increased recipient morbidity, chronic allograft nephropathy and increased medical costs has however tempered DCD kidney utilization in this country. Development of strategies that limit normothermic reperfusion injury, promote renal repair, reduce the incidence and/or duration of DGF and improve long-term outcome can greatly enhance acceptance and recruitment of DCD kidneys. The study is designed to evaluate the safety and efficacy of an intravenously administered drug in recipients of kidneys from DCD donors who are risk for developing DGF. This trial is unique in that it compares drug versus placebo outcome in kidney recipients from the same donor with direct evaluation of function (creatinine clearance) in the graft.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht
    • Minderbroedersberg, Maastricht, Netherlands, 6211 LK
      • Maastricht University Medical Center
• Spain
  • Madrid
    • San Carlos, Madrid, Spain, 28001
      • Hospital Clinico San Carlos
• United Kingdom
  • metropolitan county of Tyne and Wear
    • Newcastle, metropolitan county of Tyne and Wear, United Kingdom, NE7 7DN
      • The Newcastle Upon Tyne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Subjects must sign the informed consent document prior to performance of any study related procedure including the Screening procedure.
2. Males and females ≥ 18 years of age.
3. Had renal transplantation due to end stage disease requiring chronic dialysis.
4. Study drug can be administered within 6 to 36 hours after transplantation.
5. Received kidney from donor after cardiac death.
6. DCD kidney fulfills the clinical site's criteria for transplantation.
7. Creatinine clearance from the transplanted kidney over a 2-hour collection period is <10 mL/min, OR 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 24 hours after transplantation to pre-transplantation is < 30%.
8. Dry weight ≤ 100 kg.
9. Women of child bearing potential have a negative 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 study period; a condom with spermicide is considered a single barrier.
11. In the opinion of the Investigator, the subject is capable of understanding and complying with the protocol.

Exclusion Criteria

1. Mean arterial pressure <40 mmHg or cardiac index <1.8 L/min/m2.
2. Recipient of multiple organ transplantation or scheduled for multiple organ transplantation.
3. Recipient of kidney from a pediatric donor age 10 years or less.
4. Recipient age > 75 years.
5. Patients with ASA 4 or 5
6. Patients with chronic obstructive pulmonary disease (COPD) GOLD IV
7. Has measurable donor-specific antibody or positive cross-match requiring deviation from standard immunosuppressive therapy.
8. 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 enrolment into this study.
9. Concurrent sepsis or active bacterial infection.
10. 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.
11. Women of child bearing potential who is breast feeding.
12. History of positive HIV test.
13. History of rheumatoid arthritis.
14. History of proliferative retinopathy or laser surgery for retinopathy.
15. Subjects who have a penicillin allergy.
16. Subjects who require the cytochrome P450 1A2 (CYP1A2) inhibitors, or are receiving ciprofloxacin and fluvoxamine (Luvox®).
17. Subject is unwilling or unable to comply with the protocol or to cooperate fully with the Investigator or the site personnel.
18. 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	Drug: Normal Saline; Daily intravenous administration for four (4) days. The volume of normal saline will vary by estimated weight.
Active Comparator: BB3; Small molecule mimetic of hepatocyte growth factor/scatter factor	Drug: BB3; Daily intravenous administration of 2mg/kg for 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
creatinine clearance	The primary analysis to assess the activity of BB3 compared to placebo will be the mean difference in creatinine clearance over time using selective 24-hour urine collections from the transplanted kidney from the first infusion of study drug through day 7 post-transplant.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospitalization following transplantation	Length of hospitalization following transplantation	28 days
Urine production	Median time (days) until production of ≥1 litre urine over a 24-hour period, i.e. median number of days following the first infusion of study drug until the first day (08:00 - 08:00) that urine production was ≥1 litre over a 24-hour period.	28 days
Creatinine clearance	Calculated creatinine clearance at days 14 and 28	28 days
Incidence of delayed graft function	Incidence of delayed graft function (required dialysis due to inadequate renal function during the first 7 days after transplantation).	7 days
Number of dialysis sessions	Number of dialysis sessions through day 7, 14, and 28	28 days
Mean total daily urine output	Mean total daily urine output through day 14	14 days
Daily serum creatinine	Daily serum creatinine at days 1 to 7	7 days
Mean serum creatinine	Mean serum creatinine at days 4, 7, 10, 14, and 28	28 days
Follow-up on graft survival and function	Results of the 6- and 12-month follow-up on graft survival and function will be summarized as an addendum to the final clinical study report	12 months

Collaborators and Investigators

• Sponsor: Angion Biomedica Corp
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): May 1, 2016

Study Registration Dates

• First Submitted: March 21, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 23, 2012

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 18, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Kidney transplantation; hepatocyte growth factor mimetic; hepatocyte growth factor(HGF); Delayed Graft Function (DGF)
• Additional Relevant MeSH Terms: Pathologic Processes; Delayed Graft Function
• Other Study ID Numbers: 004-09; 2010-019243-19 (EudraCT Number); 2R44DK078455-02 (U.S. NIH Grant/Contract)