Systemic Lupus Erythematosus (SLE) MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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 contraception including at least one method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of participants who achieve SRI (6), SRI (4), and SRI (8), proportion of participants 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), 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;Main Objective: • To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of participants who achieve systemic lupus erythematosus responder index (SRI) (4);Primary end point(s): 1. Percentage of participants who achieve SRI (4) at Week 52;Timepoint(s) of evaluation of this end point: 1. At Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants who achieve SRI (6) at Week 52 2. Percentage of participants 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 (8) at Week 52 6. Percentage of participants who achieve SRI (4) at Week 24 7. Percentage of participants who achieve clinical SRI (4) at Week 52 8. Percentage of participants who achieve SRI (4) at Week 52 on low-dose corticosteroids 9. Percentage of participants who achieve LLDAS at Week 52 10. Time to first BILAG flare over 52 weeks 11. Change in FACIT-F scale from baseline to Week 52 12. Change in SF-36 v2 Bodily Pain domain scale from baseline to Week 52 13. Change in SF-36 v2 Physical Component Summary scale from baseline to Week 52 14. 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) 15. Percentage of participants with adverse events of special interest, including, among others, infusion-related reactions (IRRs), neutropenia, infections, and thrombocytopenia 16. Change from baseline in targeted vital signs 17. Change from baseline in targeted clinical laboratory test results 18. Serum concentration of obinutuzumab at specified timepoints 19. Prevalence of anti-drug antibodies (ADAs) against obinutuzumab at baseline 20. Incidence of ADAs against obinutuzumab during the study;Timepoint(s) of evaluation of this end point: 1. At Week 52 2-3. From Week 40 to Week 52 4-5. At Week 52 6. At Week 24 7-9. At Week 52 10. Up to Week 52 11-13. Baseline (Day 1) to Week 52 14-15. Through completion of Study Follow Up 16-17. Baseline (Day 1) through completion of Study Follow Up 18. Double blind period: At Weeks 2, 4, 12, 24, 26, 36, 52 and at early study dis | — |
Countries
Argentina, Australia, Brazil, France, Italy, Mexico, New Zealand, Peru, Poland, Russian Federation, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed