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 |
Lupus Nephritis is an inflammation of kidneys caused by systemic lupus erythematosus, an autoimmune disease (body’s immune system targets its own body tissues) that can affect any part of the body. |
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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 | 21.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that secukinumab 300 mg is superior to placebo in Complete Renal Response (CRR) rate at Week 52 in active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing Class V features) subjects on a background of SoC therapy.
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E.2.2 | Secondary objectives of the trial |
To demonstrate superiority of secukinumab compared to placebo in:
Change from baseline in 24-hour Urine Protein-to Creatinine ratio (UPCR) at Week 52;
Proportion of subjects achieving Partial Renal Response (PRR) at Week 52;
Average daily dose of oral corticosteroids administered between Week 16 and Week 52;
Proportion of subjects achieving PRR at Week 24;
Tine to achieve CRR;
Time to achieve PRR;
Time to achieve first morning void UPCR ≤ 0.5 mg/mg;
Change in FACIT-Fatigue© score at Week 52;
Patient’s health related quality of life via Medical Outcome Short Form Health Survey (SF-36 Physical Component Summary (PCS)) score at Week 52;
Change of Lupus QoL score at Week 52;
To evaluate the safety and tolerability of secukinumab s.c. as an add-on therapy to Standard of Care in lupus nephritis subjects;
To estimate the proportion of subjects with maintained response at Week 104;
To estimate the proportion of subjects with improved or maintained response at Week 104 |
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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 |
1) Biomarkers (2019-10-11, Version 00):
Study includes additional, optional biomarker components. These optional assessments aim to identify potential markers of response and/or loss of response, and to characterize molecular mechanisms of treatment with secukinumab. Serum and urine biomarkers related to autoimmunity, renal inflammation and renal tissue injury will be measured.
2) Pharmacogenetics: blood samples for DNA and RNA analyses (2019-10-11, Version 00):
The genetic research is optional. The purpose of genetic research is to evaluate effect of genetic polymorphisms on treatment response and to better understand the safety and efficacy of secukinumab. |
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E.3 | Principal inclusion criteria |
1. Adult male and female subjects aged 18 - 75 years old at the time of Baseline.
2. Confirmed diagnosis of:
- SLE as defined by the American College of Rheumatology (ACR), OR
- LN as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.
3. Active lupus nephritis:
- International Society of Neurology/Renal Pathology Society (ISN/RPS) Class III or IV LN [excluding III (C), IV-S (C) and IV-G (C)]; subjects are permitted to have co-existing Class V.
- UPCR ≥1 at Screening.
- Estimated Glomerular Filtration Rate (eGFR) >30 mL/min/1.73 m2.
- Active urinary sediment.
Other protocol-defined inclusion criteria may apply |
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E.4 | Principal exclusion criteria |
1. Severe renal impairment and subjects requiring dialysis within the previous 12 months before Screening.
2. Significant medical Problems like myocarditis, pericarditis, severe manifestations of neuropsychiatric SLE (NPSLE).
3. Cyclophosphamide (CYC) use (i.v. or oral) or more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within the month prior to Baseline.
4. Active ongoing inflammatory diseases.
5. Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor.
6. Ongoing infections or malignant process.
7. Pregnant or lactating women.
Other protocol-defined exclusion criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving 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. Change in 24-hour Urine Protein-to Creatinine Ratio (UPCR) at Week 52
2. Proportion of patients achieving Partial Renal Response (PRR) at Week 52
3. Average daily dose of oral corticosteroids administered between Week 16 and Week 52 compared to placebo
4. Proportion of patients achieving PRR at Week 24
5. Time to achieve CRR from Baseline to Week 52
6. Time to achieve PRR from Baseline to Week 52
7. Time to achieve first morning void UPCR ≤ 0.5 mg/mg from Baseline to Week 52
8. Change in FACIT-Fatigue©, mean change of score compared to placebo from Baseline to Week 52
9. Change in SF-36 PCS mean change compared to placebo from Baseline to Week 52
10. Change in LupusQoL mean change of score compared to placebo from Baseline to Week 52
11. Incidence of Treatment-emergent AEs (TEAEs) / SAEs from Baseline to Week 52; vital signs and body measurements, standard chemistry and hematology from Baseline to Week 52
12. Estimate the proportion of subjects with CRR at Week 104 within subjects who had achieved CRR at Week 52 in the secukinumab group (Week 52 to Week 104)
13. Estimate the proportion of subjects with improved or mainatined response (PRR or CRR) in patients who had achieved at least PRR at week 52 in the secukinumab group |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 52
2. Week 52
3. Week 16 to Week 52
4. Week 24
5. Baseline to Week 52
6. Baseline to Week 52
7. Baseline to Week 52
8. Baseline to Week 52
9. Baseline to Week 52
10. Baseline to Week 52
11. Baseline to Week 52
12. Week 52 to Week 104
13. Week 52 to Week 104 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 58 |
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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Guatemala |
India |
Japan |
Korea, Republic of |
Mauritius |
Mexico |
Peru |
Philippines |
Russian Federation |
South Africa |
Taiwan |
Thailand |
Turkey |
United States |
Vietnam |
Croatia |
Czechia |
Denmark |
France |
Germany |
Greece |
Italy |
Latvia |
Norway |
Portugal |
Romania |
Slovakia |
Spain |
Sweden |
Switzerland |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |