Lupus Nephritis
Conditions
Brief summary
This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics (PK) of obinutuzumab in adolescent participants (AP) aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN). It will also evaluate open label safety and PK of obinutuzumab in pediatric participants (PP), aged 5 to \<12 with LN.
Interventions
DRUGObinutuzumab
Obinutuzumab will be administered by IV infusion at a dose of 1000 mg on Day 1, Day 14, Week 24, Week 26 and Week 52.
DRUGPlacebo
Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.
DRUGMycophenolate Mofetil
Mycophenolate Mofetil (MMF) will be taken by home administration orally at a target dose of 1200 mg/m\^2/day to a maximum of 2.5g/day from baseline (Day 1) onwards.
Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.
Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.
DRUGMethylprednisolone
Methylprednisolone 80 mg IV will be administered as pre-medication prior to infusions.
DRUGPrednisone
Oral prednisone or equivalent corticosteroid will be taken by home administration daily to a maximum dose of 60mg/day followed by a guided taper to 5mg/day or less by Week 24.
Sponsors
Hoffmann-La Roche
Genentech, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participants who are age 12 to \<18 years at the time of randomization * Participants who are age 5 to \<12 years (younger participant cohort) at the time of randomization once recruitment is open. (Investigators will be notified by the Sponsor when recruitment is open to this younger population) * International Society of Nephrology and the Renal Pathology Society (ISN/RPS) 2003 Class III or IV active LN demonstrated on renal biopsy performed in the 12 months prior to or during screening * Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible * Diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria * Significant proteinuria defined by a UPCR above \> 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.
Exclusion criteria
* Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia * Sclerosis in \>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 * 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 or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinoma and squamous cell carcinoma of the skin that have been excised and cured) within the past 5 years * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP) | Week 76 | CRR is defined as achievement of all of the following: * Urinary protein-to-creatinine ratio (UPCR) \<0.5 g/g * Estimated Glomerular Filtration Rate (eGFR) \>=85% of baseline * No occurrence of intercurrent events |
| Percentage of Participants with Adverse Events (PP) | Baseline to Week 76 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a CRR (AP) | Weeks 24 and 52 | — |
| Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP) | Week 76 | — |
| Percentage of Participants who Achieve a PRR (AP) | Week 76 | — |
| Percentage of Participants Achieving an Overall Response (CRR or PRR) (AP) | Weeks 24, 52, and 76 | PRR is defined as: achievement of all of the following: * \>=50% reduction in urinary protein-to-creatinine ratio (UPCR) from baseline * UPCR \< 1 g/g (or \< 3 g/g if the baseline UPCR was \>=3 g/g) * eGFR \>=85% of baseline * No occurrence of intercurrent events |
| Change in UPCR (AP) | Baseline to Week 76 | — |
| Change in eGFR (AP) | Baseline to Week 76 | — |
| Time to Onset of CRR over the Course of 76 weeks (AP) | Up to Week 76 | — |
| Percentage of Participants who Experience Treatment Failure (AP) | Week 12 to Week 76 | — |
| Change in anti-dsDNA titers (AP) | Baseline to Week 76 | — |
| Change in C3 Complement Levels (AP) | Baseline to Week 76 | — |
| Change in C4 Complement Levels (AP) | Baseline to Week 76 | — |
| Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP) | Baseline to Week 76 | — |
| Serum Concentrations of Obinutuzumab (AP) | Baseline to Week 76 | — |
| Percentage of Participants Achieving B-cell Depletion (AP) | Baseline, Weeks 4, 24, 52 and 76 | — |
| Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP) | Baseline to Week 76 | — |
| Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP) | Baseline to Week 76 | — |
| Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP) | Baseline to Week 76 | — |
| Percentage of Participants with Anti-drug Antibodies (ADA) (AP) | Weeks 0, 24, 52 and 76 | — |
| Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP) | Weeks 24, 52 and 76 | — |
| Percentage of Participants Achieving a CRR (PP) | Week 76 | — |
| Percentage of Participants Achieving an Overall Response (PP) | Week 76 | PRR is defined as achievement of all of the following: * \>=50% reduction in UPCR from baseline * UPCR \< 1 g/g (or \< 3 g/g if the baseline UPCR was \>=3 g/g) * eGFR \>=85% of baseline * No occurrence of intercurrent events |
| Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP) | Week 76 | — |
| Change in eGFR (PP) | Baseline to Week 76 | — |
| Percentage of Participants Achieving B-cell Depletion (PP) | Baseline, Weeks 4, 24, 52 and 76 | — |
| Percentage of Participants with ADAs (PP) | Weeks 0, 24, 52 and 76 | — |
| Change in anti-dsDNA titers (PP) | Baseline to Week 76 | — |
Countries
Brazil, Canada, France, Italy, Mexico, Peru, Poland, Russia, South Africa, Spain, United Kingdom, United States
Contacts
CONTACTReference Study ID Number: WA42985 https://forpatients.roche.com/
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed