E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025140 |
E.1.2 | Term | Lupus nephritis |
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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 |
To evaluate the safety and tolerability of two doses of laquinimod (0.5 mg and 1 mg/day), in subjects with active Lupus Nephritis in combination with standard of care (MMF and steroids). To evaluate biomarkers and clinical effect of two doses of laquinimod (0.5 mg and 1 mg/day), in subjects with active Lupus Nephritis in combination with standard of care (MMF and steroids).
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The following sub-study is described in the same Sponsor' protocol LN-LAQ-201:
Voluntary participation in a pharmacogenetic sub-study:
A single sample of approximately 6ml of blood will be collected only once during the study.
The objective of this pharmacogenetic study is to collect and store DNA samples for use in future exploratory analyses for the assessment of possible associations between genetic polymorphisms and response to laquinimod.
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E.3 | Principal inclusion criteria |
1.Subjects diagnosed with SLE, who fulfilled at least 4 classification criteria of the American College of Rheumatology for SLE by the time of screening visit. 2.Kidney biopsy within 6 months prior to baseline with a histological diagnosis of LN. 3.Clinically active LN 4.Subjects must be between the ages of 18 and 75 years (inclusive). 5.Subjects are willing and able to provide a written informed consent.
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E.4 | Principal exclusion criteria |
1.GFR ≤ 30 ml/min/1.73m2 as calculated by MDRD formula at screening visit. 2.Dialysis within the last month prior to screening or scheduled to receive dialysis. 3.Previous kidney transplant or planned transplant. 4.Subjects with hemoglobin < 8.5 g/dl or neutrophils < 1300/ mm3 or platelets < 50,000/mm3 at screening. 5.Any previous diagnosis of drug induced lupus. 6.Subjects with severe, unstable and/or progressive CNS lupus and/or associated with significant cognitive impairment. 7.Subjects with a clinically significant or unstable medical or surgical condition that, in the Investigator’s opinion, would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests or imaging. 8. MMF/steroids specific exclusion criteria: Pancreatitis within 6 months prior to screening. Gastrointestinal hemorrhage within 6 months prior to screening. Peptic ulcers (unhealed) within 3 months prior to screening Subject weight > 120kg (265 pound). 9. Subjects with a ≥ 2.5x upper limit of normal (ULN) serum elevation of either ALT or AST at screening. 10.Subjects with a ≥ 2x upper limit of normal direct or total bilirubin at screening. 11.Subjects diagnosed with Diabetes Mellitus, or Anti-Neutrophil Cytoplasmic Antibodies (ANCA) Vasculitis. 12.Medical condition, other than SLE that requires chronic treatment with immunosuppressive drugs or systemic corticosteroids (not including inhaled steroids). 13.Subjects with a history of malignancy within 5 years from screening with the exception of basal cell carcinoma (completely excised). 14.Women who are pregnant or nursing at the time of screening, or who intend to be during the study period. 15.Women of child-bearing potential who do not practice an acceptable method of birth control. 16.Subjects treated with MMF dose ≥ 2 g/day anytime between 31 days and 90 days prior to baseline or MMF dose >2 g/day within 30 days prior to baseline. 17.Subjects treated with oral corticosteroids at doses higher than 20 mg/day of prednisolone/prednisone (or equivalent) anytime between 8 and 90 days prior to baseline or prednisolone/prednisone dose (or equivalent) >40 mg/day within 7 days prior to baseline or any IV or IM steroid dose within 90 days prior to baseline. 18.Subjects treated with Azathioprine, MTX, Cyclosporine or Tacrolimus within 2 weeks prior to baseline. 19.Subjects treated with cyclophosphamide within 12 weeks prior to screening. 20.Subjects treated with Rituximab, abatacept, intravenous immune globulin (IV Ig), plasmapheresis or any other biologic therapy within 24 weeks prior to screening. 21.Subjects treated with alkylating agents (other than cyclophosphamide such as: nitrogen mustard, chlorambucil, vincristine, procarbazine or etopside) within 52 weeks prior to screening. 22.Subjects who received any investigational medication within 24 weeks prior to screening. 23.Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for fluoxetine). 24.Use of amiodarone within 2 years prior to screening visit. 25.A known drug hypersensitivity that would preclude administration of study medications, such as known hypersensitivity to MMF, corticosteroids or hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate. 26.Subjects unable to comply with the planned schedule of study visits and study procedures.
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E.5 End points |
E.5.1 | Primary end point(s) |
This study is exploratory in nature; therefore, no formal statistical hypothesis testing is planned. |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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.8.3 |
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 | 5 |
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 |
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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
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The study will be completed upon completion of the 4 weeks follow up period following 24 weeks of treatment. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |