E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
renal recipients |
niertransplantaatontvangers |
|
E.1.1.1 | Medical condition in easily understood language |
patient who received a renal transplant |
niertransplantaatontvangers |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A 6-month study of efficacy and safety comparing concentration-controlled Certican® with MSCs to Certican® with standard tacrolimus in renal transplant recipients
Patients of the MSC treated groups will receive two doses of autologous bone marrow (BM) derived MSCs IV, 7 days apart, 6 and 7 weeks after transplantation in combination with Certican® (1.5 mg/day). At the time of the second MSC infusion tacrolimus will be withdrawn in 2 weeks (after 1 week dose of tacrolimus will be halved, after 2 weeks stopped). Doses of MSCs will be 1-2x106 million MSCs per/kg body weight. Patients in the control group will receive Certican® (1.5 mg/day) and standard dose tacrolimus (through levels 6-8 ng/ml after 6 weeks).
The primary end point is to compare fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups at 6 months compared
to 4 weeks post transplant. |
Een 6 maand durende studie hetgeen de effectiviteit en veieligheid vergelijkt tussen concentratie-gecontroleerd Certican® met MSCs tov Certican® met standaard dosis tacrolimus in niertransplantaat ontvangers
Vergelijking van fibrose door kwantitatieve Sirius Red scoring in MSC behandelde en onbehandelde groep op 6 maanden vergeleken met 4 weken na transplantatie |
|
E.2.2 | Secondary objectives of the trial |
Composite end point efficacy failure (Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up) at 6 months; renal function measured by cGFR (MDRD formula and iohexol clearance) and proteinuria at 6 months; CMV and BK infection (viremia, disease and syndrome); adverse events; the presence of donor specific antibodies (DSA) and immune monitoring in the different treatment groups; to compare the progression of "subclinical" cardiovascular disease in the different treatment groups by assessing echocardiography and pulse wave velocity. |
Eind punt effectiviteit falen (Biopsy Proven Acute Rejection (BPAR), graft verlies, dood of verlies follow-up) op 6 maaden; nierfucntie gemeten met cGFR (MDRD formule en iohexol) en proteinuria op 6 maanden; CMV and BK infectie (viremia, ziekte en syndroom); adverse events; the aanwezigheid van donor specifieke antibodies (DSA) en immune monitoring in de verschillende behandelgroepen; progressie van "subklinische" cardiovasculaire ziekte in de verschillende groepen dmv echocardiography and pulse wave velocity. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female or male, aged between 18 and 75 years.
2. Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure.
3. Recipients of a first kidney graft from a deceased, living-unrelated or non-HLA identical living related donor > 50 years of age.
4. Panel Reactive Antibodies (PRA) ≤ 10%.
5. Patients must be able to adhere to the study visit schedule and protocol requirements.
6. If female and of child-bearing age, subject must be non-pregnant, non-breastfeeding, and use adequate contraception.
|
1. Man/vrouw, tussen 18 en 75 jaar
2. Bereid zijn mee te doen aan de studie, mogelijkheid informed consent te geven hetgeen verkregen meot zijn voor de studie
3. Ontvangers van een eerste niertransplantaat, van een overleden, of levende noet HLA identieke levende donor> 50 jaat
4. PRA <10%
5. Patienten moeten het studieschema kunnen volgen en de protocol eisen
6. Geen zwangerschap, adequate anticonceptie |
|
E.4 | Principal exclusion criteria |
1. Double organ transplant recipient.
2. Biopsy proven acute rejection (according to the Banff criteria) after transplantation.*
3. Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion.*
4. Patients suffering from hepatic failure.*
5. Patients suffering from an active autoimmune disease.*
6. Patients who have had a previous BM transplant.
7. A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
8. Use of any investigational drug after transplantation.
9. Documented HIV infection, active hepatitis B, hepatitis C or TB according to current transplantation inclusion criteria.*
10. Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than TB, BK) after transplantation.*
11. Malignancy (including lymphoproliferative disease) within the past 2-5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) according to current transplantation inclusion criteria.
12. Known recent substance abuse (drug or alcohol).*
13. Contraindications to undergo a BM biopsy.
14. Patients who are recipients of ABO incompatible transplants.
15. Cold ischemia time >30 hrs.
16. Patients with severe total hypercholesterolemia or total hypertriglyceridemia (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).*
|
1. Double organ transplant recipient.
2. Biopsy proven acute rejection (according to the Banff criteria) after transplantation.*
3. Patients with evidence of active infection or abscesses (with the exception of an uncomplicated urinary tract infection) before MSC infusion.*
4. Patients suffering from hepatic failure.*
5. Patients suffering from an active autoimmune disease.*
6. Patients who have had a previous BM transplant.
7. A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
8. Use of any investigational drug after transplantation.
9. Documented HIV infection, active hepatitis B, hepatitis C or TB according to current transplantation inclusion criteria.*
10. Subjects who currently an active opportunistic infection at the time of MSC infusion (e.g., herpes zoster [shingles], cytomegalovirus (CMV), Pneumocystis carinii (PCP), aspergillosis, histoplasmosis, or mycobacteria other than TB, BK) after transplantation.*
11. Malignancy (including lymphoproliferative disease) within the past 2-5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) according to current transplantation inclusion criteria.
12. Known recent substance abuse (drug or alcohol).*
13. Contraindications to undergo a BM biopsy.
14. Patients who are recipients of ABO incompatible transplants.
15. Cold ischemia time >30 hrs.
16. Patients with severe total hypercholesterolemia or total hypertriglyceridemia (patients on lipid lowering treatment with controlled hyperlipidemia are acceptable).*
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is to compare fibrosis by quantitative Sirius Red scoring of MSC treated and untreated groups at 6 months compared
to 4 weeks post transplant. |
Vergelijking van fibrose door kwantitatieve Sirius Red scoring in MSC behandelde en onbehandelde groep op 6 maanden vergeleken met 4 weken na transplantatie |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after renal transplantation |
6 months after renal transplantation |
|
E.5.2 | Secondary end point(s) |
Composite end point efficacy failure (Biopsy Proven Acute Rejection (BPAR), graft loss, death or loss to follow-up) at 6 months; renal function measured by cGFR (MDRD formula and iohexol clearance) and proteinuria at 6 months; CMV and BK infection (viremia, disease and syndrome); adverse events; the presence of donor specific antibodies (DSA) and immune monitoring in the different treatment groups; to compare the progression of "subclinical" cardiovascular disease in the different treatment groups by assessing echocardiography and pulse wave velocity. |
Eind punt effectiviteit falen (Biopsy Proven Acute Rejection (BPAR), graft verlies, dood of verlies follow-up) op 6 maaden; nierfucntie gemeten met cGFR (MDRD formule en iohexol) en proteinuria op 6 maanden; CMV and BK infectie (viremia, ziekte en syndroom); adverse events; the aanwezigheid van donor specifieke antibodies (DSA) en immune monitoring in de verschillende behandelgroepen; progressie van "subklinische" cardiovasculaire ziekte in de verschillende groepen dmv echocardiography and pulse wave velocity. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months after transplantation, and time points in between as described in the protocol |
6 maanden na niertransplantatie , en ertussen in zoals beschreven in het protocol |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
zie hierboven |
Patients of the MSC treated groups will receive two doses of autologous bone marrow (BM) derived MSC |
|
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.8.5 | The trial involves multiple Member States | No |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |