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RECRUITINGPhase 2INTERVENTIONAL

A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescents With Active Class III or IV Lupus Nephritis and the Safety and PK of Obinutuzumab in Pediatric Participants

A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescent Patients With Active Class III or IV Lupus Nephritis, Including an Evaluation of Open Label Safety and PK in a Cohort of Pediatric Patients (Aged 5 to < 12)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. Who Should NOT Join This Trial: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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

Treatments Being Tested

DRUG

Obinutuzumab

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.

DRUG

Placebo

Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.

DRUG

Mycophenolate 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.

DRUG

Acetaminophen/paracetamol

Acetaminophen 1000 mg will be administered as pre-medication prior to infusions.

DRUG

Diphenhydramine hydrochloride (HCl)

Diphenhydramine HCl 50 mg will be administered as pre-medication prior to infusions.

DRUG

Methylprednisolone

Methylprednisolone 80 mg IV will be administered as pre-medication prior to infusions.

DRUG

Prednisone

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.

Locations (20)

Loma Linda University health
Loma Linda, California, United States
UCSF Benioff Childrens Hospital
San Francisco, California, United States
Children's Hospital Colorado, Anchutz Medical Campus
Aurora, Colorado, United States
Emory Children's Center
Atlanta, Georgia, United States
Indiana University Health University Hospital
Indianapolis, Indiana, United States
Louisiana State University
Shreveport, Louisiana, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Cohen Children's Medical Center of New York
Queens, New York, United States
Cincinnati Childrens Hospital
Cincinnati, Ohio, United States
Chldren?s Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Texas Arthritis Center
El Paso, Texas, United States
Ser Servicos Especializados Em Reumatologia
Salvador, Estado de Bahia, Brazil
Centro de Pesquisa São Lucas
Campinas, São Paulo, Brazil
Hospital das Clinicas - FMUSP
São Paulo, São Paulo, Brazil
Universidade Federal de Sao Paulo - UNIFES
São Paulo, Brazil
The Hospital for Sick Children
Toronto, Ontario, Canada
Hospital Sainte-Justine
Montreal, Quebec, Canada
CH de Bicêtre
Le Kremlin-Bicêtre, France
Hôpital Robert Debré
Paris, France
Hop Necker Enfants Malades
Paris, France