Multicentre, Open Label, Randomized, Two-arm, Parallel-group Study to Assess Efficacy and Safety of ENVARSUS® Compared With Tacrolimus Used as Per Current Clinical Practice in the Initial Maintenance Setting in de Novo Kidney Transplant Patients (STEADY)

The purpose of the study is to compare tacrolimus dosing of the new Envarsus®-based immunosuppressive regimen with current clinical practice (Prograf or Advagraf) over 6 months following de novo renal transplantation in a real-life setting in different European Countries.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: ENVARSUS®; Drug: PROGRAF®; Drug: ADVAGRAF®

Detailed Description

This is a Multicentre, Open label, Randomized, Two-arm, parallel-group study to assess efficacy and safety of Envarsus® compared with tacrolimus used as per current clinical practice in the initial maintenance setting in de novo kidney transplant patients. The study will be conducted in approximately 10 european countries.

• Study Type: Interventional
• Enrollment (Actual): 428
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Parma, Italy, 43123
    • Chiesi farmaceutici Spa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient's signed informed consent obtained prior to any study-related procedure;
2. Adult men and women at least 18 years of age with end-stage renal disease who are recipients (or will be recipients) of a kidney transplant from a living or deceased donor;
3. No known contraindications to the administration of tacrolimus, other macrolides and study drugs excipients;
4. Patients must agree to use a highly reliable method of birth control;
5. Donor-recipient negative cross match test, and compatible AB0 blood type;
6. Able to swallow tablets and capsules

Exclusion Criteria:

1. Recipient of any transplanted organ other than kidney;
2. Recipient of a previous renal transplant;
3. Recipient of a kidney from a donor after cardiac death;
4. Recipient of a kidney from an AB0 incompatible or positive cross-match donor;
5. Current (not older than 3 months) anti-HLA Panel Reactive Antibody (PRA) levels higher than 30%. Whenever PRA, either complement-dependent cytotoxicity-PRA or calculated PRA , is not available, patients who are positive on solid-phase screening assay for anti-HLA antibodies must not be enrolled;
6. Recipient of a kidney with a cold ischemia time of ≥ 30 hours;
7. White blood cells count ≤ 2.8x109 cells/L unless ANC >1.0x109/L;
8. Platelet count < 50 x109 cells/L;
9. ALT or AST levels >3 times the normal upper limit during the 30 days prior transplant procedure;
10. Current abuse of drugs or alcohol;
11. Incapable of understanding purpose and risk of study, unable to give written informed consent or unwilling to comply with study protocol;
12. Treatment with any other investigational agent in the 30 days prior to enrolment;
13. Kidney recipients and/or donors positive for HCV (HCV-RNA positive or HCV-Ab positive respectively);
14. Kidney recipients and/or donors positive for HBV (HBV-DNA or HBS-Ag positive);
15. Recipients positive for HIV;
16. Patient or donor with current diagnosis or history of malignancy within the past 5 years except basal or non-metastatic squamous cell carcinoma of the skin successfully treated;
17. Uncontrolled concomitant infection, systemic infection requiring treatment or any other unstable condition that could interfere with study objectives;
18. Severe diarrhoea, vomiting, active peptic ulcer or GI disorder that may affect absorption of tacrolimus;
19. Known hypersensitivity to tacrolimus other macrolides and study drugs excipients;
20. Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are willing to use reliable methods of contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Envarsus® (tacrolimus); prolonged-release tablets once daily and orally	Drug: ENVARSUS®; Envarsus® tablets, once daily, oral formulation. Prolonged -release formulation of tacrolimus
Active Comparator: Prograf or Advagraf; Prograf® hard capsules, twice daily, oral formulation or Advagraf® prolonged-release hard capsules, once daily, oral formulation	Drug: PROGRAF®; Prograf® hard capsules, twice daily, oral formulation; Drug: ADVAGRAF®; Advagraf® prolonged-release hard capsules, once daily, oral formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tacrolimus total daily dose (TDD) from week 3 to month 6	from week 3 to month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Tacrolimus blood trough level (TL).	from screening to months 6
number of dose adjustment	from screening to months 6
Occurrence of treatment failure	from screening to months 6
Delayed graft function	from screening to months 6
Acute rejection requiring treatment	from screening to months 6
Consumption of concomitant immunosuppressant medications	from screening to months 6
Treatment discontinuation	from screening to months 6

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Klemens Budde, MD, Berlin, Germany

Publications and helpful links

General Publications

• Budde K, Rostaing L, Maggiore U, Piotti G, Surace D, Geraci S, Procaccianti C, Nicolini G, Witzke O, Kamar N, Albano L, Buchler M, Pascual J, Gutierrez-Dalmau A, Kuypers D, Wekerle T, Glyda M, Carmellini M, Tisone G, Midtvedt K, Wennberg L, Grinyo JM. Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus in de novo Kidney Transplant Patients Across Europe. Transpl Int. 2022 Mar 21;35:10225. doi: 10.3389/ti.2021.10225. eCollection 2022.

Helpful Links

• Study Record on EU Clinical Trials Register including results

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): January 24, 2017
• Study Completion (Actual): January 24, 2017

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 4, 2015

Study Record Updates

• Last Update Posted (Actual): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 12, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: CCD-06235AA1-01; 2014-004314-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED