E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
systemic lupus erythematosus |
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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 | 21.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025139 |
E.1.2 | Term | Lupus erythematosus systemic |
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 |
The primary objective of this study is to demonstrate efficacy of BIIB059 compared with placebo in participants with active systemic lupus erythematosus (SLE), who are receiving background lupus standard of care (SOC) therapy in reducing disease activity. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: * to demonstrate: - early onset of efficacy of BIIB059 compared with placebo in participants with active SLE, receiving SOC in reducing disease activity; - organ-specific efficacy of BIIB059 compared with placebo in participants with active SLE, receiving SOC in reducing joint disease activity; - effect of BIIB059 compared with placebo in reducing oral corticosteroid (OCS) use; - organ-specific efficacy of BIIB059 compared with placebo in participants with active SLE receiving SOC in reducing skin disease activity and in reducing occurrence of flare up to Week 52; *to evaluate: - additional efficacy of BIIB059 compared with placebo in reducing disease activity with additional disease activity measures and OCS use - the safety, tolerability and immunogenicity of BIIB059 in participants with active SLE; * to assess the difference between BIIB059 and placebo on participant-reported HRQoL, symptoms, and impacts of SLE; |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: - Participant must be diagnosed with SLE at least 24 weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, at screening by a qualified physician. - Participant has a modified Systemic Lupus Erythematosus Disease Activity Index-200 (SLEDAI-2K) score ≥6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated). - Participant has a modified clinical SLEDAI-2K score ≥4 (excluding anti-dsDNA, low complement component 3 [C3] and/or complement component 4 [C4], alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated) and randomization. - Participant has BILAG-2004 grade A in ≥1 organ system or BILAG-2004 grade B in ≥2 organ systems at screening (adjudicated) and randomization. - Participants must be treated with one of the following background nonbiologic lupus SOC therapies, initiated ≥12 weeks prior to screening and at stable dose ≥4 weeks prior to randomization, a. Antimalarials as stand-alone treatment b. Antimalarial treatment in combination with OCS and/or a single immunosuppressant c. Treatment with OCS and/or a single immunosuppressant. Note: Other protocol defined inclusion criteria may apply. |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: - History of or positive test result for human immunodeficiency virus (HIV). - Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibody and detectable HCV ribonucleic acid [RNA]). - Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]). - History of severe herpes infection. - Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure. - Active severe lupus nephritis where, in the opinion of the investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach, such as adding intravenous (IV) cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated; or urine protein-creatinine ratio >2.0 or severe chronic kidney disease (estimated glomerular filtration rate <30 milliliters per minute per 1.73 meter square [mL/min/1.73 m^2]) calculated using the abbreviated Modification of Diet in Renal Disease equation. - Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-induced lupus. - History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome. - Active neuropsychiatric SLE. - Use of oral prednisone (or equivalent) above 20 mg/day. Note: Other protocol defined Exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants Who Achieved a Systemic Lupus Erythematosus Responder Index of 4 (SRI-4) Response at Week 52 |
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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. Percentage of Participants Who Achieved an SRI-4 Response at Week 24 2. Percentage of Participants With at Least 4 Joints (Both Swollen and Tender) at Baseline Who Achieved a Joint-50 Response at Week 52 3. Percentage of Participants with OCS ≥10 milligrams per day (mg/day) at Baseline Who Have OCS Reduction to ≤7.5 mg/day at Week 40, Which Is Sustained Through Week 52 with No Disease Worsening from Week 40 to Week 52 4. Percentage of Participants with a CLASI-A Score ≥10 at Baseline Who Achieved a 50% Improvement from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity Score (CLASI-50) Response at Week 16 5. Annualized Flare Rate Through Week 52 6. Change from Baseline in Physician's Global Assessment (PGA) - Visual Analog Scale (VAS) Score by Visit 7. Percentage of Participants Who Achieved a British Isles Lupus Activity Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response by Visit 8. Time to Onset of SRI-4 Response Sustained Through Week 52 9. Percentage of Participants Who Achieved SRI-4, -5, or -6 Response by Visit 10. Percentage of Participants with Joint-50 Response by Visit 11. Percentage of Participants with Baseline CLASI-A Score ≥10 Who Achieved a CLASI- 20, -50, -70, or -90 Response by Visit 12. Percentage of Participants with Baseline CLASI-A Score ≥10 Who Achieved a CLASI-A Score of ≤1 by Vis 13. Time to First British Isles Lupus Activity Group-2004 (BILAG-2004) Severe Flare by Visit 14. Time to first severe SFI flare during the double blind, placebo-controlled treatment period, where severe flare is defined using the SFI definition 15. Percentage of time spent in LLDAS. 16. Proportion of participants with sustained LLDAS as defined by the number of participants with ≥ 3, ≥ 5, and ≥ 7 consecutive visits in LLDAS up to and including Week 52. 17. Proportion of participants who achieved LLDAS at Week 52. 15. Percentage of Participants with Baseline OCS ≥10 mg/day Who Achieved ≤7.5 mg/day at Week 52 16. Change from Baseline in Lupus-Specific Health-Related Quality-of-Life Questionnaire (LupusQoL) Score 17. Change from Baseline in Short Form Health Survey-36 (SF-36) Score 18. Change from Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-Fatigue) Score 19. Change from Baseline in Patient Health Questionnaire-9 (PHQ-9) Score 20. Change from Baseline in Work Productivity and Activity Impairment (WPAI): Lupus Score 21. Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) 22. Number of Participants with Antibodies to BIIB059 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. wk 24 2. wk 52 3. wk 40 up to wk 52 4. wk 16 5. up to wk 52 6. up to wk 52 7. up to wk 52 8. up to wk 52 9. up to wk 52 10. up to wk 52 11. up to wk 52 12. up to wk 52 13. up to wk 52 14. up to wk 52 15. wk 52 16. up to wk 52 17. up to wk 52 18. up to wk 52 19. up to wk 52 20. up to wk 52 21. up to wk 52 22. up to wk 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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 |
immunogenicity and tolerability |
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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 | 3 |
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 | 35 |
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 |
Colombia |
Canada |
China |
Israel |
Japan |
Serbia |
United Kingdom |
United States |
Belgium |
Czechia |
Germany |
Hungary |
Italy |
Netherlands |
Romania |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 4 |