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

Phase 1

Conditions: ESRD (end stage renal disease)
MedDRA version: 19.0Level: LLTClassification code 10050436Term: Prophylaxis against renal transplant rejectionSystem Organ Class: 100000004865
Therapeutic area: Body processes [G] - Immune system processes [G12]

Registration Number: EUCTR2014-004314-29-DE

Lead Sponsor: Chiesi Farmaceutici S.p.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 400

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 of the following reliable methods of contraception:
a. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
b. Hormonal contraception (implantable, injectable, patch, oral)
c. Double barrier methods of contraception: condom and occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository
The use of diaphragm is allowed only if in combination with a chemical contraceptive (ie, ointments, gels, suppositories, tablets, foam or sprays that contain spermicides). Condoms must not be used with lubricant and oils.
d. Male sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
21. Persons who have been housed in an institution due to a government or judicial order;
22. Persons who are dependent on the sponsor, the investigator or the trial site

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Tacrolimus total daily dose (TDD);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.<br><br>• To describe the current tacrolimus-based immunosuppressive strategies for renal transplantation as for local clinical practice in different European Countries<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Tacrolimus trough level (TL);<br>- Tacrolimus total daily dose (TDD) normalized for weight (mg/kg)<br>- Number of dose adjustments;<br>- Treatment failure rate, time to treatment failure;<br>- Proportion of patients with local diagnosis of acute rejection requiring<br>treatment;<br>- Proportion of patients with delayed graft function<br>- Daily dose and consumption of concomitant immunosuppressant<br>medications<br>Safety variables<br>- Incidence of Adverse Events and Serious Adverse Events;<br>- Incidence of Adverse Drug Reactions (ADR) and Serious Adverse Drug<br>Reactions;<br>- Proportion of patients with Post-Transplant Diabetes Mellitus (PTDM);<br>- Incidence of any opportunistic infection;<br>Health Resources:<br>- Scheduled and unscheduled tacrolimus plasma levels determinations;<br>- Unscheduled hospitalizations and tests.;Timepoint(s) of evaluation of this end point: by visit (weekly - to month 6) except for treatment failure collected throughout duration.

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