Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01950819
• Date of registration: 20/08/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Advancing Renal TRANSplant eFficacy and Safety Outcomes With an eveRolimus-based regiMen (TRANSFORM) TRANSFORM
• 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
• Date of first enrolment: December 3, 2013
• Target sample size: 2037
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01950819
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

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

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

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.

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 to drugs of similar chemical
classes.

4. Multi-organ transplant recipient.

5. Recipient of ABO incompatible allograft or complement-dependent lymphocytotoxic (CDC)
crossmatch positive transplant.

6. Subject at high immunological risk for rejection as determined by local practice for
assessment of anti-donor reactivity e.g. high PRA, presence of pre-existing DSA.

7. Subject who is HIV-positive.

8. HBsAg and/or a HCV positive subject with evidence of elevated LFTs (ALT/AST levels =
2.5 times ULN). Viral serology results obtained within 6 months prior to randomization
are acceptable.

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. Subject with a BMI greater than 35.

11. Subject with severe systemic infections, current or within the two weeks prior to
randomization.

12. Subject requiring systemic anticoagulation.

13. History of malignancy of any organ system.

14. Subject with severe restrictive or obstructive pulmonary disorders.

15. Subject with severe hypercholesterolemia or hypertriglyceridemia that cannot be
controlled.

16. Subject with 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, defined as all women physiologically capable of
becoming pregnant, unless they are using effective methods of contraception during
dosing of study treatment.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Kidney Disease (CKD)

Hemodialysis

Renal Replacement Therapy

Renal Transplantation

End Stage Renal Disease (ESRD)

Intervention(s)

Biological: Induction therapy

Drug: EVR+rCNI

Drug: MPA+sCNI

Drug: Corticosteroids

Primary Outcome(s)

Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2. [Time Frame: Month 12 is Primary, Month 24 secondary]

Secondary Outcome(s)

Incidence of Composite of tBPAR (Treated Biopsy-proven Acute Rejection)or eGRF<50 mL/Min/1.73m2 by Subgroup [Time Frame: Month 12 and 24]

Incidence of Death, Graft Loss, tBPAR, BPAR, tAR, AR and Humoral Rejection [Time Frame: Month 12 and 24]

Renal Function by Alternative Formulae (e.g. CKD-EPI). eGFR Values Reported [Time Frame: Month 12 and 24]

Urinary Protein and Albumin Excretion by Treatment Estimated by Urinary Protein/Creatinine and Urinary Albumin/Creatinine Ratios. [Time Frame: Baseline, Month 12 and 24]

Incidence of tBPAR (Treated Biopsy-proven Acute Rejection) Excluding Grade IA Rejections [Time Frame: Month 12 and 24]

Incidence of eGFR < 50 mL/Min/1.73m2 [Time Frame: Month 12 and 24]

Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death or Loss to Follow-up [Time Frame: Month 12 and 24]

Evolution of Renal Function, as eGFR, Over Time by Slope Analysis. [Time Frame: Month 12 and 24]

Incidence of Adverse Events, Serious Adverse Events and Adverse Events Leading to Study Regimen Discontinuation. [Time Frame: Month 24]

Incidence of Cytomegalovirus and BK Virus, New Onset Diabetes Mellitus, Chronic Kidney Disease With Associated Proteinuria and Calcineurin Inhibitor Associated Adverse Events. [Time Frame: Month 24]

Incidence of Failure on the Composite Endpoint of Graft Loss or Death. [Time Frame: Month 12 and 24]

Incidence of Failure on the Composite Endpoint of tBPAR, Graft Loss, Death or eGFR < 50 mL/Min/1.73m2 [Time Frame: Month 12 and 24]

Incidence of Failure on the Composite of (Treated Biopsy Proven Acute Rejection (tBPAR), Graft Loss or Death [Time Frame: Month 12 and 24]

Incidence of Failure on the Composite of Treated Biopsy-proven Acute Rejection (tBPAR) or Estimated Glomerular Filtration Rate (eGFR) < 50 mL/Min/1.73m2 Among Compliant Subjects. [Time Frame: Month 12 and 24]

Incidence of tBPAR (Excluding Grade IA Rejections) or GFR<50 mL/Min/1.73m2 [Time Frame: Month 12 and 24]

Renal Allograft Function : Mean Estimated Glomerular Filtration Rate, eGFR [Time Frame: Baseline (week 4), Month 12 and 24]

Incidence of Malignancies. [Time Frame: Month 24]

Incidence of Major Cardiovascular Events. [Time Frame: Month 24]

Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Events) [Time Frame: Month 12 and 24]

Renal Function Assessed by Creatinine Lab Values [Time Frame: Month 12 and 24]

Incidence tBPAR (Treated Biopsy-proven Acute Rejection) by Severity and Time to Event (Participants) [Time Frame: Month 12 and 24]

Secondary ID(s)

CRAD001A2433

2013-000322-66

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/01/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01950819