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 |
SLE is an autoimmune disease in which the immune system attacks its own tissues, causing tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys and blood vessels. |
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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.1.3 | 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 of obinutuzumab compared with placebo based on proportion of participants who achieve systemic lupus erythematosus responder index (SRI) (4) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of participants who achieve SRI (6) and SRI (4) proportion of participants entering the study on prednisone >= 10 mg/day (or equivalent) who achieve sustained corticosteroid control, proportion of participants who achieve British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), proportion of participants who achieve Lupus Low Disease Activity State (LLDAS), DORIS, time to first British Isles Lupus Assessment Group (BILAG) flare, change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale from baseline, change in 36-Item Short Form Survey, Version 2 (SF-36 v2) Bodily Pain domain scale from baseline and change in SF-36 v2 Physical Component Summary scale from baseline • To evaluate the safety of obinutuzumab compared with placebo • To characterize the obinutuzumab pharmacokinetics (PK) profile • To evaluate the immune response to obinutuzumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participants who are age 18-75 years at the time of signing Informed Consent Form • Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria >=12 weeks prior to screening • Anti-nuclear antibody (ANA) >=1:80, or anti-dsDNA and/or anti-Sm antibodies above the upper limit of normal (ULN), as determined by the central laboratory at screening • Low C3, C4, and/or CH50 as determined by the central laboratory at screening • High disease activity at screening, based on; BILAG-2004 (level A disease in >=1 organ system and/or Level B disease in >=2 organ systems), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (score >=8) and Physician’s Global Assessment (PGA) (score >=1.0 on a 0 to 3 visual analogue scale [VAS]) • High disease activity on Day 1, based on; SLEDAI-2K (score >=8) and PGA (score >=1.0 on a 0 to 3 VAS) • Current receipt of >=1 of the following classes of standard therapies for the treatment of SLE at stable doses: oral corticosteroid (OCS), antimalarials, conventional immunosuppressants • For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception method including at least one method with a failure rate of <1% per year, during the treatment period and for 18 months after the final dose of obinutuzumab or placebo • The Medical Monitor may be consulted if there are any questions related to eligibility criteria |
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E.4 | Principal exclusion criteria |
• Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo • Presence of significant lupus-associated renal disease and/or renal impairment • Active severe or unstable lupus-associated neuropsychiatric disease or where, in the opinion of the investigator, it is likely to require treatment with protocol-disallowed therapies • Active overlap syndrome with mixed connective tissue disease or systemic sclerosis within 12 months prior to screening or during screening • Catastrophic or severe antiphospholipid syndrome within 12 months prior to screening or during screening • History of non-SLE inflammatory skin or joint disease within one year of Day 1 that, in the opinion of the investigator, could interfere with assessments of skin or joint manifestations of SLE • History of any non-SLE disease treated with oral, intravenous (IV), or intramuscular (IM) corticosteroids for more than 14 days in total during the one year prior to Day 1 • Receipt of any of the following excluded therapies: a) Any B-cell depleting (e.g., anti-CD20, anti-CD19) or anti-plasma cell therapy such as, but not limited to, obinutuzumab, rituximab, ocrelizumab, ofatumumab, or bortezomib less than 9 months prior to screening or during screening; b) Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening; c) Any biologic therapy (other than anti-CD20, anti-CD19, or anti-plasma cell) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening; d) Inhibitors of Janus-associated kinase (JAK), Bruton’s tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening; e) Any live vaccine during the 28 days prior to screening or during screening • High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions • Significant or uncontrolled medical disease which, in the investigator’s opinion, would preclude patient participation • Human immunodeficiency virus (HIV) infection • Tuberculosis (TB) infection • Active infection of any kind, excluding fungal infection of the nail beds • Any major episode of infection • History of serious recurrent or chronic infection • History of progressive multifocal leukoencephalopathy (PML) • History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years • Major surgery requiring hospitalization during the 4 weeks prior to screening or during screening • Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening • Intolerance or contraindication to study therapies |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Percentage of participants who achieve SRI (4) 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 achieve SRI (6) at Week 52 2. Percentage of participants entering the study on prednisone >= 10 mg/day (or equivalent) who achieve Sustained Corticosteroid Control from Week 40 through Week 52 3. Percentage of participants who achieve Sustained SRI (4) response from Week 40 through Week 52 4. Percentage of participants who achieve BICLA at Week 52 5. Percentage of participants who achieve SRI (4) at Week 24 6. Percentage of participants who achieve clinical SRI (4) at Week 52 7. Percentage of participants who achieve SRI (4) at Week 52 on low-dose corticosteroids 8. Percentage of participants who achieve LLDAS at Week 52 9. Percentage of participants who achieve definition of remission in SLE (DORIS) at Week 52 10. Time to first BILAG flare over 52 weeks 11. Change in FACIT-F scale from baseline to Week 24 and from baseline to Week 52 12. Change in SF-36 v2 Bodily Pain domain scale from baseline to Week 24 and from baseline to Week 52 13. Change in SF-36 v2 Physical Component Summary scale from baseline to Week 24 and from baseline to Week 52 14. Change in active joint count (swollen plus tender) from baseline to Week 24 and from baseline to Week 52 15. Proportion of participants who achieve a >= 50% reduction in active joint counts (swollen plus tender) at each study visit, among participants with >= 4 active joints at baseline 16. Proportion of participants who achieve a >= 50% reduction in CLASI Total Activity Score at each study visit, among participants with CLASI Total Activity Score >= 10 at baseline 17. Proportion of participants who achieve sustained corticosteroid control from Week 40 through Week 52 18. Cumulative corticosteroid use (in equivalent milligrams of prednisone) through Week 52 19. Annualized flare rate through Week 52 20. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 21. Percentage of participants with adverse events of special interest, including, among others, infusion-related reactions (IRRs), neutropenia, infections, and thrombocytopenia 22. Change from baseline in targeted vital signs 23. Change from baseline in targeted clinical laboratory test results 24. Serum concentration of obinutuzumab at specified timepoints 25. Prevalence of anti-drug antibodies (ADAs) against obinutuzumab at baseline 26. Incidence of ADAs against obinutuzumab during the study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At Week 52 2-3. From Week 40 to Week 52 4. At wk 52 5. At wk 24 6-9. At wk 52 10. Up to wk 52 11-14. Baseline (Day 1) to wk 24 and from baseline to wk 52 15-16. At wks 0, 2, 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52 17. At wk 40 and wk 52 18-19. At wk 52 20-21. Through completion of Study Follow Up 22-23. Baseline (Day 1) through completion of Study Follow Up 24. Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 58, 66, 78, 80, 90, 104 and at early study discontinuation visit 25. Baseline (Day 1) 26. Double blind period: At Weeks 2, 4, 12, 24, 26, 52 and at early study discontinuation visit; Open label period: At Weeks 54, 56, 66, 78, 80, 104 and at early study discontinuation visit |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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) | 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
New Zealand |
Peru |
Australia |
Brazil |
Mexico |
Russian Federation |
South Africa |
United Kingdom |
United States |
Czechia |
France |
Italy |
Poland |
Spain |
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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 end of this study is defined as the date of the scheduled last participant, last visit (LPLV) or when all participants are discontinued from the study, whichever occurs earlier. No further study follow up visits will occur after the following date: 18 months after all participants have completed or discontinued study drug infusions (blinded and open-label). The end of the study is expected to occur approximately 3 years after the last participant is enrolled. |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |