Pediatric patients that received a transplanted kidney will receive immunosuppressive medication-the calcineurin inhibitor (tacrolimus) and antiproliferative agent (MMF)-until they will be randomized between week 4 and 6 to receive either the same treatment or to switch to the investigational drug everolimus. The patients will be followed up until 3 years after transplantation to evaluate the efficacy, tolerability and safety of the treatments and to assess their impact on renal function.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-024381-21-DE
• Date of registration: 28/12/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Pediatric patients that received a transplanted kidney will receive immunosuppressive medication-the calcineurin inhibitor (tacrolimus) and antiproliferative agent (MMF)-until they will be randomized between week 4 and 6 to receive either the same treatment or to switch to the investigational drug everolimus. The patients will be followed up until 3 years after transplantation to evaluate the efficacy, tolerability and safety of the treatments and to assess their impact on renal function.
• Scientific title: A 12-month, multicenter, open label, randomized, controlled study to evaluate the efficacy, tolerability and safety of early introduction of everolimus, reduced CNI, and early steroid elimination compared to standard CNI, mycophenolate mofetil and steroid regimen in paediatric renal transplant recipients with a 24-month additional safety follow-up - not applicable
• Date of first enrolment: 07/05/2012
• Target sample size: 106
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024381-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, France, Germany, Hungary, Italy, Norway, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

• Name: Medical Competence Center
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
Inclusion criteria at baseline (transplantation)
1. Written informed consent/assent must be obtained from the parent(s) or legal guardian
before any assessment is performed.
2. Primary or secondary paediatric kidney transplant recipient aged greater than or equal to 1
year and younger than 18 years receiving a primary deceased donor or non-HLA identical
living donor (related or unrelated) renal transplant.
Inclusion criteria at randomization (4-6 weeks after transplantation)
1. Patients on TAC + MMF + steroids.
2. Renal function with eGFR > 50 40 ml/min/1.73 m2 (Schwartz formula - abbreviated).
Are the trial subjects under 18? yes
Number of subjects for this age range: 106
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients fulfilling any of the following criteria are not eligible for inclusion in this study at
baseline
1. Recipients of kidneys from donors with known renal disease (such as diabetices
nephropathy, nephrosclerosis), at the time of transplant.
2. Recipients of a kidney with a cold ischemia time > 24 hours.
3. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 halflives
of enrollment, whichever is longer.
4.3. History of hypersensitivity or contraindication to any of the study drugs or to drugs of
similar chemical classes, or to any of the excipients.
5.4. History of malignancy of any organ system treated or untreated, carrying possible risk
of recurrence according to current guidelines (Appendix 10). within the past 5 years,
regardless of whether there is evidence of local recurrence or metastases.
6.5. Pregnant or nursing (lactating) female patients, where pregnancy is defined as the state
of a female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 9 mIU/mL).
7.6. Female patients of child-bearing potential, defined as all women physiologically
capable of becoming pregnant, UNLESS they agree for to abstinence from sexual activity.
8.7. Patients who are recipients of multiple solid organ transplants, including dual and en
bloc kidneys, or who have previously received transplanted organs except a primary
kidney transplant.
9.8. Recipient of kidneys from HLA-identical living related donors.
This document (090095a8846f511b in docbase CREDI_BS) has been digitally signed with external signatures using Entrust PKI.
Signatures manifested as of 3/4/2013 8:16:30 AM, signing status at this time: Completed (1 of 1 signatures)
Approved for report publication by Martzloff El-Djouher in Basel at Mon, Mar 04, 2013 09:16:13 CET
Novartis Confidential Page 28
Amended Protocol Version v02 track changes Protocol CRAD001A2314
10.9. Recipients of kidneys from donors who are greater than 60 years or younger than 5
years.
11.10. Recipient of ABO incompatible allograft or a positive T cell cross-match.
12.11. Most recent anti-HLA Class I/II panel reactive antibodies > 20 % by a Complement
Dependent Cytotoxicity (CDC)-based assay or > 50% by a flow cytometry or Enzyme
Linked Immunosorbent Assay (ELISA)-based assay.
13.12. Patients considered at high risk of antibody mediated acute rejection (e.g. presence of
pre-formed DSA) (as the DSA quantitative threshold to define high risk is not fully
established, the assessment of the risk will be made after discussion between the
laboratory expert and the investigator who will take into account all information available
and apply best judgment).
14.13. Patient who is human immunodeficiency virus (HIV) positive or Hepatitis C (PCR
only) or B surface antigen positive. Viral serology

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Prevention of acute rejection in paediatric recipients of a renal transplant
MedDRA version: 19.0 Level: SOC Classification code 10038359 Term: Renal and urinary disorders System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Certican
Product Name: Certican 0,25 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Certican
Product Name: Certican 0,5 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Certican
Product Name: Certican 0,75 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: Certican
Product Name: Certican 1 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Certican
Pr

Primary Outcome(s)

Secondary Objective: - To evaluate each of the components of the composite efficacy endpoint
- To evaluate the time to event and severity of BPAR
- To evaluate incidence of biopsy proven antibody mediated rejection
- To Evaluate the incidence/progression of chronic allograft nephropathy (Interstitial Fibrosis and Tubular Atrophy IF/TA) by histopathology.
- To evaluate growth and development, including linear growth, sexual maturation, hormonal gonadal axis (estradiol, testosterone, LH, FSH, inhibin B), TSH, T3 and T4

Primary end point(s): 1- The incidence of composite efficacy failure including BPAR, death, and graft loss at 12 months. Local biopsy readings will be used to determine the occurrence of BPAR.
2- Renal function will be assessed by eGFR estimated by the Schwartz formula (abbreviated) at month 12.

Timepoint(s) of evaluation of this end point: Month 12 after transplantation.

Main Objective: - To estimate the rate of the composite efficacy endpoint of BPAR, graft loss or death at 12 months post transplantation in primary paediatric kidney transplant recipients converted at 4-6 weeks post-transplantation from MMF + standard TAC regimen and steroids, to everolimus + reduced dose TAC regimen and steroid withdrawal at 6 months, versus continuation of MMF + standard TAC regimen and steroids.
- To evaluate renal function assessed by Glomerular Filtration Rate (eGFR) estimated by the Schwartz formula (abbreviated) at month 12.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Month 12 and 36 after transplantation.

Secondary end point(s): 1- Components of the composite efficacy endpoint;
2- Incidences of biopsy proven antibody mediated rejection
3- Incidence/progression of chronic allograft nephropathy (interstitial fibrosis and tubular atrophy, IF/TA);
4- Safety (evolution of renal function over time, incidence of proteinuria, the frequency of drug-related side effects (CNI-related, mTOR-inhibitor-specific or MMF-class effects), assessment of growth and development, the frequency of AEs/Infections, SAEs.

Secondary ID(s)

CRAD001A2314

2010-024381-21-HU

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 04/04/2019
• Date Completed: 24/09/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-024381-21/results