Study investigating a standard treatment in kidney transplant patients versus a treatment with Certican® in combination with Cyclosporin A or Tacrolimus

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2011-005238-21-DE
• Date of registration: 20/03/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: Study investigating a standard treatment in kidney transplant patients versus a treatment with Certican® in combination with Cyclosporin A or Tacrolimus
• Scientific title: 12 month, multi-center, open-label, prospective, randomized, parallel group study investigating a standard regimen in de novo kidney transplant patients versus a Certican® based regimen either in combination with Cyclosporin A or Tacrolimus - ATHENA
• Date of first enrolment: 17/10/2012
• Target sample size: 612
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-005238-21
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female renal allograft recipients at least 18 years old
2. Patient who has received a primary or secondary kidney transplant from a deceased or living unrelated-/related donor
3. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
4. Recipient of a kidney allograft with a cold ischemia time (CIT) < 30 hours
5. Female patients who are menstruating and capable of becoming pregnant must have a negative pregnancy test prior to study enrollment

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
2. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
3. Patients receiving a kidney from a non-heart beating donor
4. Patients who are recipients of A-B-0 incompatible transplants
5. Patients with a current Panel Reactive Antibody (PRA) level of > 20% (PRA levels within 4 months prior to enrollment) or patients with a positive Luminex test for any antigen of the donor
6. Patients with already existing antibodies against the HLA-type of the receiving transplant (in the knowledge of the investigator at the time point of transplantation)
7. Patients with a known hypersensitivity/contraindication to any of the immunosuppressants or their classes, or to any of the excipients
8. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
9. Patients with thrombocytopenia (platelets < 100,000/mm³), with an absolute neutrophil count of < 2,000/mm³ or leucopenia (leucocytes < 3,000/mm³), or hemoglobin < 8 g/dL
10. Patients with symptoms of significant mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent
11. Patients with a history of malignancy during the last five years, except squamous or basal cell carcinoma of the skin, renal cell carcinoma = T1N0M0, prostate adenocarcinoma = T1N0M0 and adenocarcinoma of the thyroid
12. Patients who are HIV positive
13. Patient with uncontrolled hypercholesterolemia or hypertriglyceridemia
14. Evidence of drug or alcohol abuse
15. Women
o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml))
o who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women entering menarche is required with sufficient lead time before inclusion
*definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy
**examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe:
? Combination pill with estrogen and gestagen (no mini-pill, PI=0.1-0.9)
? Vaginal ring (PI=0.65 uncorr.; 0.4 corr.)
? Contraceptive patch (PI= 0.72 uncorr.; 0.9 corr.)
? Estrogen-free ovulation inhibitors (PI=0.14)
? Progestin-containing contraceptives (PI=0-0.08)
? Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
? Intra-uterine progestine device (PI=0.16)
Highly effective contraception methods include:
? Total abstinence (when this is in line with the preferred and usual lifestyle of the
subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.


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

Health Condition(s) or Problem(s) studied

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

Kidney transplantation
MedDRA version: 17.0 Level: LLT Classification code 10054990 Term: Immunodeficiency secondary to organ transplantation System Organ Class: 100000004870

Intervention(s)

Trade Name: Certican Tabletten
Product Code: RAD001
Pharmaceutical Form: Tablet
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-

Trade Name: Certican Tabletten
Product Code: RAD001
Pharmaceutical Form: Tablet
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Certican Tabletten
Product Code: RAD001
Pharmaceutical Form: Tablet
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.75-

Trade Name: Certican Tabletten
Product Code: RAD001
Pharmaceutical Form: Tablet
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Pharmaceutical Form: Capsule, hard
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Pharmaceutical Form: Capsule, hard
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Pharmaceutical Form: Capsule, hard
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5.0-

Pharmaceutical Form: Capsule, soft
CAS Number: 59865-13-3
Other descriptive name: Cyclosporine A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Pharmaceutical Form: Capsule, soft
CAS Number: 59865-13-3
Other descriptive name: Cyclosporine A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Pharmaceutical Form: Capsule, soft
CAS Number: 59865-13-3
Other descriptive name: Cyclosporine A
Concentration unit: mg m

Primary Outcome(s)

Main Objective: To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard group at month 12 post-transplantation in renal transplant patients.

Primary end point(s): The primary efficacy variable of this trial is the renal function at Visit 7/Month 12 after randomization as assessed by estimated glomerular filtration rate (eGFR) based on recalculated values according to the Nankivell formula.

Secondary Objective: • To assess renal function by means of glomerular filtration rate at Month 12 post-transplantation
• To assess the incidence of individual endpoints BPAR, graft loss and death at Month 12 post-transplantation
• To assess the incidence and severity of viral infections
• To assess the incidence and duration of Delayed Graft Function
• To assess the incidence of Slow Graft Function defined as serum creatinine > 3,0 mg/dl at day 5
• To assess the incidence of wound healing complications related to the surgery
• To assess the duration of healing
• To compare the overall safety and tolerability at Month 12 post-transplantation

Timepoint(s) of evaluation of this end point: at 12 month

Secondary Outcome(s)

Secondary end point(s): The following secondary efficacy variables will be analyzed in an explorative manner for the full analysis set (FAS):
• Key secondary objective is to assess the incidence of treatment failure (combinded endpoint of BPAR, graft loss or death).

Additional secondary objectives are:
• To assess the incidence of individual components of the combined efficacy endpoint, that is BPAR, graft loss and death at Month 12 post-transplantation.
• To assess renal function by cGFR according to the CKD-EPI, Cockcroft-Gault and MDRD methods, respectively.
• To assess the incidence and duration of Delayed Graft Function.
• To assess the incidence of Slow Graft Funtion.
• To assess safety and tolerability during the study, especially the incidence and severity of viral infections (CMV, BKV), the incidence of wound healing complications, and the incidence of Left Ventricular Hypertrophy (LVH) .

Timepoint(s) of evaluation of this end point: at 12 month

Secondary ID(s)

CRAD001ADE44

Source(s) of Monetary Support

Novartis Pharma GmbH