E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from end-stage renal disease, receiving a donor kidney from donors after cardiac death |
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E.1.1.1 | Medical condition in easily understood language |
Patients suffering from end-stage renal disease, receiving a donor kidney from donors after cardiac death |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014647 |
E.1.2 | Term | End stage renal failure |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the safety and efficacy of BB3 compared to placebo in improving renal function in the immediate post-transplant period in patients who have received DCD (Donor after Cardiac Death) kidney transplantation. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To take advantage of the availability of non-paired kidneys, a sub-study of non-paired kidneys will be performed for 10 patients. |
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E.3 | Principal 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. |
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Creatinine clearance (CrCl) over time, as assessed by selective 24-hour urine collections from the donor kidney, starting from the first infusion of the study drug, to day 7 post-transplant. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Every 24 hours from time of first infusion of the study drug to day 7 post-transplant. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Median time (days) until production of ≥1 liter urine over a 24-hour period - Calculated creatinine clearance at days 14 and 28 - Incidence of delayed graft function (required dialysis due to inadequate renal function) during the first 7 days after transplantation - Number of dialysis sessions through day 7, 14, and 28 - Mean total daily urine output through day 14 - Daily serum creatinine at days 1 to 7 and at days 1 to 14 - Mean serum creatinine at days 4, 7, 10, 14, and 28 - Length of hospitalization following transplantation - Results of the 6- and 12-month follow-up on graft survival and function
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the last patient’s last visit, i.e. the completion of the 12 month follow up visit by the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 29 |