To evaluate the safety and activity of BB3 compared to placebo in improving renal function in the immediate post-transplant period in patientswho have received a DCD kidney transplantation.
ID
Source
Brief title
Condition
- Nephropathies
- Renal and urinary tract therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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. If a subject
has more than one creatinine value assessed during the 24-hour urine
collection, the mean of the values will be used for calculation of
creatinine clearance.
Secondary outcome
Safety
Pharmacokinetics
Incidence of delayed graft function
Mean urine output
number of acute rejections
hospitalstay
Background summary
Kidney transplantation from donors after cardiac death (DCD) is associated with
a high risk for delayed graft function (DGF) due to ischemic
acute kidney injury (AKI). BB3 is a small-molecule hepatocyte growth factor
mimetic that has been shown to improve early graft function after
kidney transplantation in rats and dogs.
Study objective
To evaluate the safety and activity of BB3 compared to placebo in improving
renal function in the immediate post-transplant period in patients
who have received a DCD kidney transplantation.
Study design
The primary intent is a paired-kidney design. This means that both recipients
must participate in the study. In some cases, this isn*t possible. For example:
if both kidneys are allocated to our centre, it is possible that the first
recipient gives consent and is included in the study. This recipient will be
randomized to receive either BB3 or placebo, while the second recipient is not
yet available for consent. If the second recipient doesn*t want to participate,
the first recipient, who already got the first infusion, would be excluded,
according to the paired-kidney study design. Inclusion of an unpaired-kidney
recipient will allow inclusion of these subjects into the analysis.
Intervention
One group receives 4 intravenous infusions of 2 mg/kg BB3 at 6-9, 24±3, 48±3
and 72±3 hours following kidney transplantation and the other
group receives an equal volume of normal saline at the same time points.
Study burden and risks
Participation in this trial requires 40 additional blood samples (2.5 ml), 7
additional spot urine samples (10 ml), 7 additional 24-hour urine
collections, no additional site visits, 1 medical history, 2 full physical
examinations, 8 abbreviated physical examinations, 2 fundoscopic
examinations, 9 electrocardiograms and no questionnaires. If a subject is
discharged prior to day 28 after transplantation, the subject will receive a
'urine' diary to record the daily volume of urine up to and including day 14
and on day 28 after transplantation.
Infusion of the study drug was well tolerated in healthy volunteers and
dialysis patients. At the dose used in this study, no toxic effects of the drug
were observed in rats and dogs. Patients will benefit from participating if BB3
indeed improves early graft function after DCD kidney transplantation.
Charles Lindbergh Boulevard 51
Uniondale NY 11553
US
Charles Lindbergh Boulevard 51
Uniondale NY 11553
US
Listed location countries
Age
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 < 50 cc/H over a 24 hour period, OR normal urine output following transplantation that diminished to < 50 cc/H over a 24 hour period 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-019243-19-NL |
| CCMO | NL31820.068.10 |