Lupus Nephritis
Conditions
Interventions
Trade Name: Gazyvaro
Product Name: Obinutuzumab
Product Code: RO5072759/F06-01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Curr
Sponsors
Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Age 18?75 years ? Diagnosis of SLE, according to current American College of Rheumatology criteria ? Diagnosis of ISN/RPS 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months prior to screening. Patients may co-exhibit Class V disease in addition to either Class III or Class IV disease. ? Patients must demonstrate active urinary sediment as evidenced by >=10 red blood cells/high power field or the presence of red cell casts. ? Proteinuria (urine protein to creatinine ratio) >1.0 ? For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate 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 12
Exclusion criteria
Exclusion criteria: ? Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE ? Presence of rapidly progressive glomerulonephritis ? Severe renal impairment as defined by estimated GFR <30 milliliter per minute or the need for dialysis or renal transplant ? Greater than 50% of glomeruli with sclerosis on renal biopsy ? Treatment with cyclophosphamide or calcineurin inhibitors within the 3 months prior to randomization ? Unstable disease with thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions ? History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion ? Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator?s opinion, would preclude patient participation ? Concomitant chronic conditions, excluding SLE, (e.g., asthma, Crohn?s disease) that required oral or systemic steroid use in the 52 weeks prior to screening ? History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinomas of the skin that have been treated or excised and have resolved)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To evaluate the efficacy of obinutuzumab compared with placebo in patients with International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Class III or IV Lupus Nephritis (LN) as measured by complete renal response (CRR) at 52 weeks;Secondary Objective: ? To assess the ability of obinutuzumab to induce overall renal response and to improve time-to-response over the course of 52 weeks ? To evaluate the safety of obinutuzumab compared with placebo in patients with Class III or IV LN ? To characterize the immunogenic potential of obinutuzumab by measuring human anti-drug antibodies and assessing their relationship with other outcome measures ? To fully characterize adverse events of special interest, including infusion reactions, infections, thrombocytopenia, and neutropenia ? To compare changes in CD19+ B cells in the peripheral blood following treatment with obinutuzumab versus placebo ? To characterize the pharmacokinetics of obinutuzumab in the LN population and assess potential PK interactions between obinutuzumab and concomitant medications ? To assess the change from baseline of the patient?s general health over the course of the study by use of the Patient?s Global Assessment;Primary end point(s): 1. Number of patients who achieve complete renal response (CRR) at Week 52;Timepoint(s) of evaluation of this end point: 1. Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of patients who achieve overall response at Week 52 2. Number of patients who achieve partial renal response (PRR) at Week 52 3. Time to first overall response over the course of 52 weeks 4. Number of patients who achieve CRR at Week 24 5. Percent change from baseline in biomarkers of LN disease activity 6. Time to CRR over the course of 52 weeks 7. Number of patients who achieve a modified CRR (mCRR1) at Week 52 8. Number of patients who achieve a second mCRR (mCRR2) at Week 52 9. Change in Patient's Global Assessment from baseline to Week 52;Timepoint(s) of evaluation of this end point: 1. Week 52 2. Week 52 3. Baseline (Day 1) to Week 52 4. Week 24 5. At screening (Day -28 to -1), Week 1 (before infusion), Week 2, Week 4, Week 12, Week 24 (before infusion), Week 36, Week 52, Week 76, and Week 104 6. Baseline (Day 1) to Week 52 7. Week 52 8. Week 52 9. Baseline (Day 1), Week 4, Week 12, Week 24, Week 36, Week 52 | — |
Countries
Brazil, Colombia, France, Germany, Israel, Italy, Mexico, Spain, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed