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• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2013-000322-66-IT
• Date of registration: 12/08/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Farma SpA
• Public title: NA
• Scientific title: A 24 month, multicenter, randomized, open-label safety and efficacy study of concentration-controlled everolimus with reduced calcineurin inhibitor vs mycophenolate with standard calcineurin inhibitor in de novo renal transplantation - Advancing renal TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen (TRANSFORM) - Advancing renal TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen (TRANSFORM)
• Date of first enrolment: 30/09/2013
• Target sample size: 2040
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000322-66
• 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): no Therapeutic use (Phase IV): yes

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Colombia, Croatia, Czech Republic, Egypt, France, Germany, Greece, Guatemala, India, Indonesia, Italy, Japan, Jordan, Korea, Republic of, Kuwait, Lebanon, Malaysia, Mexico, Netherlands, Norway, Panama, Philippines, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United States, Venezuela, Bolivarian Republic of

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Farma SpA

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Farma SpA

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent obtained.

2. Subject randomized within 24 hr of completion of transplant surgery.

3. Recipient of a kidney with a cold ischemia time < 30 hours.

4. Recipient of a primary (or secondary, if first graft is not lost due to immunological reasons) renal transplant from a deceased heart beating, living unrelated, living related non-human leukocyte antigen identical or an expanded criteria donor.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2040
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
1. Subject unable to tolerate oral medication at time of randomization.
2. Use of other investigational drugs at the time of enrollment
3. History of hypersensitivity to any of the study drugs or similar chemical classes.
4. multi-organ transplant recipient
5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant
6. high immunological risk by assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA
7. HIV positive
8. HBsAg and/or a HCV positive with evidence of elevated LFTs (ALT/AST levels = 2.5 times ULN)
9. Recipient of a kidney from a donor who tests positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV)
10. BMI greater than 35
11. severe systemic infections
12. Subject requiring systemic anticoagulation
13. History of malignancy
14. severe restrictive or obstructive pulmonary disorders
15. severe hypercholesterolemia or hypertriglyceridemia
16. white blood cell (WBC) count = 2,000 /mm3 or with platelet count = 50,000 /mm3.
17. Pregnant or nursing (lactating) women
18. Women of child-bearing potential


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

Health Condition(s) or Problem(s) studied

Adult kidney transplant recipients.
MedDRA version: 16.0 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 100000004857

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

Intervention(s)

Trade Name: Certican
Product Name: Certican 0.25mg
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 0.75mg
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: Myfortic
Product Name: Myfortic 180 mg
Product Code: NA
Pharmaceutical Form: Capsule
INN or Proposed INN: MYCOPHENOLIC ACID
CAS Number: 24280-93-1
Current Sponsor code: ERL080
Other descriptive name: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 180-

Trade Name: Myfortic
Product Name: Myfortic 360
Product Code: NA
Pharmaceutical Form: Capsule
INN or Proposed INN: MYCOPHENOLIC ACID
CAS Number: 24280-93-1
Current Sponsor code: ERL080
Other descriptive name: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 360-

Trade Name: Cellcept
Product Name: Cellcept 250 mg
Product Code: NA
Pharmaceutical Form: Capsule

Trade Name: Cellcept
Product Name: Cellcept 500 mg
Product Code: NA
Pharmaceutical Form: Capsule

Primary Outcome(s)

Main Objective: Evaluate the effect of everolimus with reduced exposure CNI versus MPA with standard exposure CNI on the binary composite of treated biopsy-proven acute rejection (tBPAR) or eGFR < 50
mL/min/1.73m2 (estimated glomerular filtration rate by MDRD4 formula) at Month 12 post-transplantation.

Primary end point(s): The primary analysis will be performed on the Full Analysis Set following the intent-to-treat principle. The primary endpoint of tBPAR or eGFR (MDRD4) < 50 mL/min/1.73m2 at Month 12 will be tested at the significance level of 0.05. Event rates will be compared between groups using a 2-stage approach (hierarchical testing strategy). First, noninferiority of EVR plus reduced CNI vs. MPA plus standard CNI will be evaluated using a 10% non-inferiority margin. If this is significant, then superiority will be evaluated. Based on the closed testing principle, no multiplicity adjustment will be made for testing for both non-inferiority and superiority.

Timepoint(s) of evaluation of this end point: At 12-month after transplantation.

Secondary Objective: •composite efficacy failure rate [treated biopsy proven acute rejection(tBPAR), graft loss(GL) or death(D)] at M12
•composite endpoint(cEP)of tBPAR or eGFR<50 mL/min/1.73m2 (MDRD4) M12 among compliers
•cEPof tBPAR or eGFR<50 mL/min/1.73m2 at M24
•cEP of tBPAR (excluding Banff 1A) or eGFR<50 mL/min/1.73m2 at M24
•cEP of tBPAR or eGFR<50 mL/min/1.73m2 at M12 by subgroup
•cEP of tBPAR, GL, D, or loss to follow-up at M12/24
•cEP of tBPAR, GL, D or eGFR<50 mL/min/1.73m2 at M12/24
•individual endpoints of D, GL, tBPAR, BPAR, tAR, AR and humoral rejection at M12/24
•tBPAR by severity and time to event and also excluding excluding Banff 1A
•Tx recipients with eGFR<50 mL/min/1.73m2 at M12/24
•RF and change from M1(eGFR) at M12/24 and over time by slope analysis and by Cystatin C-based and other formulae
•AEs, SAEs and AEs leading to study drug discontinuation
•CMV and BKV, NODM, CKD with associated proteinuria and CNI associated AE
•Urinary protein/albumin excretion

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: At 12-month after transplantation.

Secondary end point(s): With respect to the key secondary endpoint - composite efficacy failure of tBPAR, graft loss or death at Month 12, non-inferiority of EVR plus reduced CNI vs. MPA plus standard CNI will be evaluated at the significance level of 0.05 using a 10% non-inferiority margin based on the Full Analysis Set.
To evaluate the binary composite endpoint of tBPAR or eGFR < 50 mL/min/1.73m2 (MDRD4) Month 12 among compliant subjects.

Secondary ID(s)

2013-000322-66-DE

CRAD001A2433

Source(s) of Monetary Support

Novartis Pharma Services AG