E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025140 |
E.1.2 | Term | Lupus nephritis |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
assess efficacy and safety of one year treatment with three different doses of BI 655064 against placebo as add-on therapy to standard of care (SOC) treatment for active lupus nephritis |
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E.2.2 | Secondary objectives of the trial |
assess the efficacy at 6 months |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
males and females 18-70 years. Women of childbearing potential* must be ready and able to use simultaneously two reliable methods of birth
control, one of which must be highly effective. Highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. The reliable contraception should be used before starting MMF therapy and the study drug, during the treatment and until 50 days after stopping MMF and the study drug. Sexually active men must be ready to use condoms during treatment with MMF and for at least 90 days after cessation of MMF treatment.
Diagnosis of systemic lupus erythematosus (SLE) by ACR criteria 1997, at least 4 criteria must be documented, one of which must be a positive anti-dsDNA antibody or a positive antinuclear antibody (ANA) at screening or around time of start of induction therapy
Lupus Nephritis Class III or IV (ISN/RPS 2003 classification) with either active or active/chronic disease, co-existing class V permitted, proven by renal biopsy within 3 months prior to screening or during screening if induction therapy has not yet been started
Active renal disease evidenced by proteinuria >= 1.0 g/day
(Uprot/Ucrea >= 1) at screening
Signed and dated written informed consent |
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E.4 | Principal exclusion criteria |
clinically significant current other renal disease
GFR<30ml/min/1.73m²
Acute presence of Oliguria (<500 mL/day)
dialysis within 12m of screening
Antiphospholipid syndrom defined as positive antiphospholipid
antibodies and either history of any thrombotic event and or history of
miscarriage.
diabetes mellitus poorly controlled or known diabethic retinopathy or
nephropathy
Evidence of current or previous clinically significant disease, medical
condition or finding in the medical examination that in the investigator's
opinion would compromise the safety of the patient or the quality of the
data
Any induction therapy for LN within the last 6 months prior to
randomisation except induction with MMF and high dose steroids tarted
within 6 weeks prior to randomisation. If a higher dose of iv steroids is considered necessary by the investigator a total dose of up to 3g is acceptable.
Treatment with any biologic B-cell depleting therapy (e.g. anti-CD20,
anti-CD22) within 12 months prior to randomisation
Treatment with Belimumab or other anti BLyS: when used for treatment
of non-renal SLE 3 months or 5 half lives whichever is longer, prior to
randomisation ; when used for treatment of Lupus nephrits: 12 months
prior to randomisation
Treatment with abatacept within 12 months prior to randomisation
Treatment with tacrolimus or cyclosporin within 4 weeks prior to
randomisation
Treatment with cyclophosphamid within 6 months prior to randomisation
Treatment with investigational drug within 6 months or 5 half-lives,
whichever is greater before randomisation
Contraindication for MMF or corticosteroids and/or known
hypersensitivity to any constituents of the study drug
Live vaccination within 6 weeks before randomisation
Chronic or relevant acute infections, including but not limited to HIV,
Hepatitis B and C and tuberculosis (including a history of clinical TB
and/or a positive QuantiFERON TB-Gold test)
Any active or suspected malignancy or history of documented
malignancy within the last 5 years before screening, except
appropriately treated carcinoma in situ and treated basal cell carcinoma.
Patients unable to comply with the protocol in the investigator¿s
opinion.
Alcohol abuse in the opinion of the investigator or active drug abuse .
Women who are pregnant, nursing, or who plan to become pregnant
while in the trial
Impaired hepatic function, defined as serum AST/ALT, bilirubin or
alkaline phosphatase levels > 2 x ULN
Significant central nervous system symptoms related to SLE based on
investigator assessment |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: proportion of patients with complete renal response
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: proportion of patients with complete renal response
2: proportion of patients with partial renal response
3: proportion of patients with major renal response
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: week 26
2: week 26 and 52
3: week 26 and 52
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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 | Yes |
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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 40 |
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 | No |
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 |
Australia |
Austria |
Canada |
Czech Republic |
France |
Germany |
Greece |
Hong Kong |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Philippines |
Poland |
Portugal |
Serbia |
Singapore |
Spain |
Thailand |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 6 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 6 |