Lupus Nephritis (LN) MedDRA version: 21.1 Level: PT Classification code 10025140 Term: Lupus nephritis System Organ Class: 10038359 - Renal and urinary 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 12 to 0.5 based on a first-morning void (FMV) collection at screening During the 12 months prior to or during screening, all participants must have received at least one dose of pulse-range IV methylprednisolone (typically 30 mg/kg, maximum of 1000 mg per dose) or equivalent for the treatment of the current episode of active LN For females of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs during the treatment period and for 18 months after the final dose of obinutuzumab and for 6 weeks after the final dose of mycophenolate mofetil (MMF) For males: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm, during the treatment period and for 90 days after the final dose of MMF Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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, or within 6 weeks after the final dose of MMF Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia Severe renal impairment, as defined by glomerular filtration rate (GFR) 50% of glomeruli on renal biopsy Purely chronic Class III(c) or Class IV(c) disease on renal biopsy, defined as the absence of any active lesions Presence of rapidly progressive glomerulonephritis Pure Class V LN Intolerance or contraindication to study therapies Receipt of any of the following excluded therapies: – Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening – Any anti-CD20 therapy such as, but not limited to, rituximab, ocrelizumab, or ofatumumab within 12 months prior to screening or during screening – Any biologic therapy (other than anti-CD20) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening – Oral 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 – Any live vaccine during the 28 days prior to screening or during screening Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe Immunodeficiency blood disorders History of serious recurrent or chronic infection History of progressive multifocal leukoencephalopathy (PML) History of or current 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 High risk for clinically significant bleeding or any condition requiring plasmapheresis, intravenous immunoglobulin, or acute blood product transfusions Significant or uncontrolled concomitant medical disease which, in the investigator’s opinion, would preclude participant participation Currently active alcohol or drug abuse or history of alcohol or drug abuse Any of the following laboratory parameters at screening: Aspartate aminotransferase (AST) or alanine transaminase (ALT) >2.5Xupper limit of normal (ULN) (for age and sex) that cannot be attributed to underlying SLE Amylase or lipase >2XULN Absolute neutrophil count (ANC) <1.5X10^3/microliter Hemoglobin <7 g/dL, unless caused by autoimmune hemolytic anemia resulting from SLE Platelet count <50,000/microliter Positive hepatitis B surface antigen (HBsAg) Positive hepatitis C serology 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 in adolescent participants with Class III/IV LN;Secondary Objective: To evaluate the efficacy of obinutuzumab compared with placebo To evaluate the safety of obinutuzumab compared with placebo To characterize obinutuzumab pharmacokinetic (PK) profile To characterize obinutuzumab pharmacodynamic (PD) profile To evaluate changes in fatigue of participants treated with obinutuzumab compared with placebo To evaluate change in SLE disease activity of participants treated with obinutuzumab compared with placebo To evaluate changes in the quality of life of participants treated with obinutuzumab compared with placebo;Primary end point(s): Proportion of participants who achieve a complete renal response (CRR) at Week 76;Timepoint(s) of evaluation of this end point: At Week 76 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of participants achieving a CRR at Weeks 24 and 52 Proportion of participants who achieve a partial renal response (PRR) at Week 76 Proportion of participants achieving an overall response (CRR or PRR) at Weeks 24, 52, and 76 Change in urinary protein-to-creatinine ratio (UPCR) from baseline to Week 76 Change in estimated glomerular filtration rate (eGFR) from baseline to Week 76 Time to onset of CRR over the course of 76 weeks Proportion of participants who experience treatment failure from Week 12 to Week 76 Change in C3 complement levels from baseline to Week 76 Change in C4 complement levels from baseline to Week 76 Incidence, nature, and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) from baseline to Week 76 Incidence of laboratory or vital sign abnormalities from baseline to Week 76 Serum concentrations of obinutuzumab at specified timepoints Proportion of participants achieving B-cell depletion via highly sensitive flow cytometry (HSFC), at specified timepoints Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue scale (PedsQL)-Fatigue total score from baseline to Week 76 Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) from baseline to Week 76 Change from baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) domain scores from baseline to Week 76;Timepoint(s) of evaluation of this end point: 1. At Weeks 24 and 52 2. At Week 76 3. At Weeks 24, 52, and 76 4-6. Baseline to Week 76 7. From Week 12 to Week 76 8-11. Baseline to Week 76 12. At Baseline and Weeks 2, 4, 12, 24, 26, 36, 52, 64, and 76 13. At Baseline and Weeks 4, 24, 52 and 76 14-16. Baseline to Week 76 | — |
Countries
Brazil, Canada, France, Italy, 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