| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective is to explore in non-inferior efficacy of Myfortic administered at a dose of 2160mg/day in combination with reduced corticosteroid regimen compared to the combination with a standard corticosteroid regimen where efficacy measure is defined as the proportion of patients in complete remission after 24 weeks of treatment |
|
| E.2.2 | Secondary objectives of the trial |
To assess/evaluate the following main (not complete list) secondary objectives:
- Proportion of patients in complete remission at 12 weeks and partial remission of lupus flares at 12 weeks and at 24 weeks.
- The corticosteroid use as cumulative dose until 12 and 24 weeks of treatment, also doses at baseline, 12 and 24 weeks
- To assess the myfortic® dose (mg/day) over time.
- Overall disease activity using BILAG and SLEDAI activity indices at weeks 4, 12 and 24
- Proportion of patients with mild SLE flare at 12 and 24 weeks and with moderate/severe SLE flare at 12 and 24 weeks
- Organ damage, utilising the SLICC/ACR Damage Index at 24 weeks
- Renal function (serum creatinine, creatinine clearance, GFR and the urine protein/ creatinine ratio
- Patients with no therapeutic response at 12 and 24 weeks
- Patients with treatment failure at 12 and 24 weeks
- Proportion of patientswith AEs, SAEs and infections during the course of the study
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- male or female with SLE (at least classification 4 of ACR)
- Aged >/ 18years
- Proliferative lupus nephritis cassified as ISN/RPS class III or IV
- Renal biopsy must be performed during the last 24 months preceding the study entry
-Proteinuria defined as >0.5g urine protein per gram urine creatinine at screening and baseline
- Clinical activity defined by one or more of the following changes in renal function:
serum creatinine>1mg/dl (88.4micromol/l),
microscopic haematuria defined as > 5 rbcs per high power field,
presence of cellular casts |
|
| E.4 | Principal exclusion criteria |
- patients with calculated creatinine clearance of < 30ml/min (using the Cockcroft-Gault formula)
- Patients having received an iv corticosteroid bolus during the last 3months
- Patients having received MMF within the preceding 3 months
-Use of any antibodies within 6 months
- Pregnant or nursing women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a positive serum β-HCG pregnancy test (> 5 mIU/ml) within 7 days prior to or at Baseline (visit 1)
- Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, including women whose career, lifestyle, or sexual
orientation precludes intercourse with a male partner and women whose partners
have been sterilized by vasectomy or other means, unless if adequate contraception is used as defined below.
WOCBP should begin using two or more of the following acceptable methods of
contraception prior to starting myfortic®, unless complete abstinence is the chosen
method. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include:
diaphragm, condom (by the partner), intrauterine device (copper or hormonal),
sponge or spermicide. Hormonal contraceptives include any marketed contraceptive
agent that includes an estrogen and/or a progestational agent. Patients should be
aware that myfortic® reduces blood levels of the hormones in the oral contraceptive
pill and could theoretically reduce its effectiveness.
Reliable contraception should start 4 weeks prior to beginning myfortic® and be
maintained throughout the study and for 6 weeks after study drug discontinuation.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation
methods) and withdrawal are not acceptable methods of contraception.
Woman are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months
of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol
< 20 pg/mL or have had surgical bilateral oophorectomy (with or without
hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when
the reproductive status of the woman has been confirmed by follow up hormone level
assessment.
- Use of other investigational drugs within 1 month of enrollment (except for antibodies within 6 months)
- History of hypersensitivity to study drugs or to drugs with similar chemical structures
- History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy variable is the complete remission rate at 24 weeks defined as the proportion of patients with urine protein/urine creatinine ratio < 0.5, urine sediment normalised and serum creatinine stable. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Study completed 7 days after the last patient has completed Visit 7. Investigator provides follow-up medical care. Study Completion CRF completed at Week 24 Patients who prematurely discontinue complete the Premature Discontinuation CRF with a subsequent follow-up evaluation form completed at Week 24, except patients prematurely discontinuing due to death, lost to follow-up or patient withdrew consent.
Follow-up visit at Week 52 will be performed in all patients. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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