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

Novartis

Status and phase: Completed; Phase 4

Conditions: Hemodialysis; Renal Replacement Therapy; Chronic Kidney Disease (CKD); Renal Transplantation; End Stage Renal Disease (ESRD)

Treatments: Biological: Induction therapy; Drug: Corticosteroids; Drug: MPA+sCNI; Drug: EVR+rCNI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01950819

CRAD001A2433

2013-000322-66 (EudraCT Number)

Details and patient eligibility

About

This is a 2-year, randomized, multicenter, open-label, 2-arm study evaluating the graft function of everolimus and reduced CNI versus MPA and standard CNI in adult de novo renal transplant recipients.

Enrollment: 2,037 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

2,037 participants in 2 patient groups

EVR+rCNI

Experimental group

Description:

Everolimus with reduced calcineurin inhibitor- everolimus (target trough level of 3-8 ng/mL) in combination with reduced exposure to CNI (cyclosporine or tacrolimus)

Treatment:

Drug: EVR+rCNI

Drug: Corticosteroids

Biological: Induction therapy

MPA+sCNI

Active Comparator group

Description:

Mycophenolate (mycophenolic acid sodium or mycophenolate mofetil) in combination with standard exposure to calcineurin inhibitor (cyclosporine or tacrolimus).

Treatment:

Drug: MPA+sCNI

Drug: Corticosteroids

Biological: Induction therapy