E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus (SLE)
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E.1.1.1 | Medical condition in easily understood language |
Systemic Lupus Erythematosus (SLE)
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue 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 evaluate the efficacy and dose response of M2951 compared to placebo in reducing disease activity in adult subjects with active, autoantibody-positive SLE who are receiving SoC therapy based on SRI-4 response at Week 52 in all subjects, or on SRI-6 response at Week 52 in the HDA subgroup, defined as SLEDAI-2K ≥ 10. - To evaluate the safety of M2951 in subjects with SLE on SoC therapy. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives: •To evaluate the efficacy and dose response of M2951 compared to placebo in delaying time to first severe flare during the Treatment Period,in subjects with SLE on SoC therapy,where a severe flare is defined as at least one BILAG 2004 A in any organ system due to items that are new or worse,compared to the BILAG evaluation at the previous visit •To evaluate the efficacy and dose response of M2951 compared to placebo in reducing disease activity,based on the SRI-4 response at W52,in the serologically active subgroup,which is defined as subjects with positive anti-dsDNA and/or low complement levels Other secondary objectives: •To evaluate the efficacy of M2951 compared to placebo on changes in disease activity and in organ-specific disease activity over52W •To evaluate the effect of M2951 compared to placebo on the annualized flare rate and on CS usage over52W •To evaluate the impact of M2951 treatment compared to placebo on subject reported HRQoL over52W |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible male and female subjects, aged 18 to 75 years; must have diagnosis of SLE with either the SLICC criteria for SLE, or at least four of the 11 ACR classification criteria for SLE, of at least six months duration prior to Screening; SLEDAI-2K total score ≥ 6 (including clinical SLEDAI ≥ 4) at Screening Visit; and and have positive test results for anti doublestranded DNA (anti-dsDNA) antibody and/or anti nuclear antibody (human epithelial cell-2 ANA ≥ 1:80) and/or anti-Smith (anti Sm) antibody at the time of Screening.
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E.4 | Principal exclusion criteria |
Subjects are not eligible for this study if they have active, clinically significant interstitial lung disease or pulmonary arterial hypertension; proteinuria (urine protein to creatinine ratio [UPCR] > 4 mg/mg); acutely worsened renal function; active central nervous system SLE (to be severe or progressive including history of transverse myelitis, seizures, and/or associated with significant cognitive impairment); or within two weeks prior to Screening or during Screening: use of oral corticosteroids > 30 mg daily prednisone equivalent; use of injectable corticosteroids, or change in dose of corticosteroids. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): All Subjects 2) Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 6 (SRI-6): High Disease Activity (HDA) Subgroup Subjects 3) Occurrences of Subjects With Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs) 4) Occurrences of Treatment-emergent Adverse Events (TEAEs) According to Severity 5) Number of Subjects With Clinically Significant Vital signs, Electrocardiogram (ECG) and Laboratory Abnormalities 6) Serum Total Immunoglobulin (Ig) levels 7) Total B Cell Counts 8) Change From Baseline to Week 56 in Serum total Immunoglobulin (Ig) levels 9) Change From Baseline to Week 56 in Total B Cell Counts
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 2: Week 52 3 to 9: Baseline up to Week 56 |
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E.5.2 | Secondary end point(s) |
1) Time to First Severe Flare 2) Number of Subjects With Response Based on Systemic Lupus Erythematosus Responder Index 4 (SRI-4): Serologically Active Subgroup |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: Baseline up to Week 52 2: Week 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 | No |
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 | 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 |
Pharmacodynamic, effect in annualized flare rate, effect corticosteroid,impact on quality of life; Health resource utilization (HRU); effects in exploratory marker.
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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 | Yes |
E.8.2.3.1 | Comparator description |
Different dosage of IMP (25mg QD, 75 mg QD, 50 mg BID) |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Brazil |
Bulgaria |
Chile |
Colombia |
Germany |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Mauritius |
Mexico |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
South Africa |
Taiwan |
United States |
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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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last contact date with the last subject who participates in this study
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 19 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 21 |