lupus nephritis MedDRA version: 21.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-75 years - Ability to comply with the study protocol, in the investigator's judgment - International Society of Nephrology / Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN by renal biopsy performed in the 6 months prior to screening or during screening - Diagnosis of SLE according to the 2019 European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) Classification Criteria, which are met by the presence of Class III or IV LN (above) and: Current or past positive antinuclear antibody (ANA), as evidenced by ANA at a titer of >= 1:80 on HEp-2 cells or an equivalent positive ANA test at least once - Urinary protein-to-creatinine ratio >= 1 on a 24-hour collection at screening - Receipt of at least one dose of pulse methylprednisolone IV (>= 250 mg) or equivalent for treatment of the current episode of active LN during the 6 months prior to screening or during screening; a maximum of 3 g methylprednisolone IV or equivalent during the 4 weeks prior to screening or during screening is allowed. - For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, women must remain abstinent or use two methods of 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 15
Exclusion criteria
Exclusion criteria: - Pregnant or breastfeeding, or intending to become pregnant during the study or within 18 months after the final dose of obinutuzumab or placebo or within 6 weeks after the final dose of MMF - Severe renal impairment, as defined by eGFR 50% of glomeruli on renal biopsy - Presence of rapidly progressive glomerulonephritis - Receipt of an excluded therapy - Severe, active central nervous system SLE, including retinitis, poorly-controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia - 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 investigators opinion, would preclude patient participation - HIV and Tuberculosis infection; latent TB after completion of appropriate treatment is not exclusionary. - Active infection of any kind, excluding fungal infection of the nail beds - Any major episode of infection that required hospitalization or treatment with IV antibiotics or anti-infectives during the 8 weeks prior to screening or during screening; antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary. - History of serious recurrent or chronic infection - History of progressive multifocal leukoencephalopathy - 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 - Laboratory parameters • AST or ALT > 2.5 × upper limit of normal (ULN) • Amylase or lipase > 2 × ULN • Neutrophils < 1.5 × 103/µL • Positive hepatitis B surface antigen (HBsAg) • Positive hepatitis C serology • Hemoglobin < 7 g/dL, unless caused by autoimmune hemolytic anemia resulting from SLE • Platelet count < 25,000/µL • Positive serum human chorionic gonadotropin measured at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of patients who achieve a complete renal response (CRR) at Week 76;Secondary Objective: • To evaluate the efficacy of obinutuzumab compared with placebo based on proportion of patients who achieve CRR with estimated glomerular filtration rate (eGFR) criterion at Week 76, overall renal response (ORR) at Week 50, change in anti-double stranded DNA antibody (anti-dsDNA) titer and C3 from baseline to Week 50, change eGFR from baseline to Week 76, change in SLE Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76, time to onset of CRR and change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) from baseline to Week 76. • To evaluate the safety of obinutuzumab compared with placebo • To characterize the obinutuzumab pharmacokinetic profile • To evaluate the immune response to obinutuzumab • To characterize the obinutuzumab-induced changes in circulating B-cells;Primary end point(s): Proportion of patients who achieve a CRR at Week 76;Timepoint(s) of evaluation of this end point: At Week 76 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of patients who achieve CRR with eGFR criterion at Week 76 2. Proportion of patients who achieve an ORR, evaluated at Week 50 3. Change in anti-dsDNA titer from baseline to Week 50 4. Change in C3 from baseline to Week 50 5. Change in SLEDAI-2K from baseline to Week 76 6. Change in eGFR from baseline to Week 76 7. Time to onset of CRR over the course of 76 weeks 8. Change in FACIT-F scale from baseline to Week 76 9. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 10. To characterize adverse events of special interest, including among others, IRRs, neutropenia, infections and thrombocytopenia. 11. Change from baseline in targeted vital signs 12. Change from baseline in targeted clinical laboratory test results 13. Maximum observed concentration (Cmax) of obinutuzumab 14. Minimum observed concentration (Cmix) of obinutuzumab 15. Area under concentration- time curve (AUC) of obinutuzumab 16. Clearance (CL) of obinutuzumab 17. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs post-treatment during the study 18. Total peripheral B-cell count at specified timepoints;Timepoint(s) of evaluation of this end point: 1. At Week 76 2. At Week 50 3-4. Baseline (Day 1) to Week 50 5-8. Baseline to Week 76 9-10. Up to 8.5 years 11-12. Baseline to 8.5 years 13-16. Baseline, Week 2, 4, 12, 24, 26, 36, 50, 64, 76, 80, 106, 132,158, 184, every 6 months thereafter, unplanned visit (UV) and at study discontinuation (SD); open label extension(OLE): Baseline, Week 2, 4, 12, 24, 26, 36, 50, 64, 76, every 6 months thereafter, UV, SD 17. Baseline, Week 2, 4, 12, 24, 36, 50, 76, 80, 106, 132,158, 184, every 6 months thereafter, UV, SD; OLE: Baseline, Week 2, 12, 24, 36, 50, 76, every 6 months thereafter, UV, SD 18. Baseline, Week 4, 12, 24, 50, 76, 80, 106, 158, UV; OLE: Baseline, Week 4, 12, 24, 52 | — |
Countries
Argentina, Brazil, Canada, Colombia, France, Germany, Israel, Italy, Mexico, 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