A study to evaluate the effect of a new medicine (Envarsus) compared to medicines used in current practice in new kidney transplant patients

• Register: EUCTR
• Last refreshed on: 8 May 2017
• Main ID: EUCTR2014-004314-29-PL
• Date of registration: 25/11/2015
• Prospective Registration: Yes
• Primary sponsor: Chiesi Farmaceutici S.p.A.
• Public title: A study to evaluate the effect of a new medicine (Envarsus) compared to medicines used in current practice in new kidney transplant patients
• Scientific title: 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 study
• Date of first enrolment: 22/12/2015
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004314-29
• 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

Austria, Belgium, France, Germany, Italy, Netherlands, Norway, Poland, Spain, Sweden, United Kingdom

Contacts

• Name: Gabriele Nicolini
• Affiliation: Chiesi Farmaceutici S.p.A.

• Name: Gabriele Nicolini
• Affiliation: Chiesi Farmaceutici S.p.A.

Key inclusion & exclusion criteria

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 ABO blood type;
6. Able to swallow tablets and capsules.
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 320
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

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 ABO incompatible donor and 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 assays 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 and/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 one or more reliable methods of contraception.


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

Health Condition(s) or Problem(s) studied

ESRD (end stage renal disease)
MedDRA version: 19.0 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865

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

Intervention(s)

Trade Name: Envarsus
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: Envarsus
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Envarsus
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Advagraf
Pharmaceutical Form: Prolonged-release capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Advagraf
Pharmaceutical Form: Prolonged-release capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Advagraf
Pharmaceutical Form: Prolonged-release capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Trade Name: Advagraf
Pharmaceutical Form: Prolonged-release capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Prograf
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: TACROLIMUS
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Co

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From week 3 to month 6.

Main Objective: To compare tacrolimus dosing of the new Envarsus®-based immunosuppressive regimen with current clinical practice over 6 months following de novo renal transplantation in a real-life setting in different European Countries.

Secondary Objective: • To evaluate the efficacy, safety and tolerability of the study treatments in terms of additional pharmacokinetic parameters and of clinical outcome measures.

• To describe the current tacrolimus-based immunosuppressive strategies for renal transplantation as for local clinical practice in different European Countries

Primary end point(s): Tacrolimus total daily dose (TDD)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: by visit (weekly - to month 6) except for treatment failure collected throughout duration.

Secondary end point(s): Tacrolimus trough level (TL);
- Tacrolimus total daily dose (TDD) normalized for weight (mg/kg)
- Number of dose adjustments;
- Treatment failure rate, time to treatment failure;
- Proportion of patients with local diagnosis of acute rejection requiring treatment;
- Proportion of patients with delayed graft function
- Daily dose and consumption of concomitant immunosuppressant medications

Safety variables
- Incidence of Adverse Events and Serious Adverse Events;
- Incidence of Adverse Drug Reactions (ADR) and Serious Adverse Drug Reactions;
- Proportion of patients with Post-Transplant Diabetes Mellitus (PTDM);
- Incidence of any opportunistic infection;

Health Resources:
- Scheduled and unscheduled tacrolimus plasma levels determinations;
- Unscheduled hospitalizations and tests.

Secondary ID(s)

CCD-06235AA1-01

N/A

2014-004314-29-BE

Source(s) of Monetary Support

Chiesi Farmaceutici S.p.A.