This study CRAD001A2433 is designed to evaluate the impact of concentration-controlled everolimus with reduced exposure CNI, compared to mycophenolic acid (MPA) with standard exposure CNI, with respect to efficacy and safety in de novo renal transplant recipients.

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)

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-000322-66-DE

Enrollment

2040

Registered

2013-08-07

Start date

2013-11-07

Completion date

Unknown

Last updated

2018-08-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adult kidney transplant recipients. MedDRA version: 19.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders

Interventions

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 descripti

Eligibility

Sex/Gender

All

Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 200

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
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.;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 ;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 evalua	—

Measure

Time frame

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.;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 ;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 evalua

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Secondary

Measure	Time frame
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.;Timepoint(s) of evaluation of this end point: At 12-month after transplantation.	—

Measure

Time frame

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

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Countries

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

Public ContactMedizinischer Infoservice (MCC)

Novartis Pharma GmbH

infoservice.novartis@novartis.com+491802232300

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026