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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

Purpose

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.

Condition

Lupus Nephritis

Eligibility

Eligible Ages: Between 5 Years and 17 Years
Eligible Sex: All
Accepts 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

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Blinded Obinutuzumab	Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).	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. Other names: Gazyva 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.
Placebo Comparator Placebo	Placebo participants will receive obinutuzumab matched placebo 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.
Experimental Open-Label Obinutuzumab	Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.	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. Other names: Gazyva 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.

Recruiting Locations

Loma Linda University health
Loma Linda, California 92354

UCSF Benioff Childrens Hospital
San Francisco, California 94158

Children's Hospital Colorado, Anchutz Medical Campus
Aurora, Colorado 80045

Emory Children's Center
Atlanta, Georgia 30322

Indiana University Health University Hospital
Indianapolis, Indiana 46202

Louisiana State University
Shreveport, Louisiana 71103

Hackensack University Medical Center
Hackensack, New Jersey 07601

Cohen Children's Medical Center of New York
Queens, New York 11042

Cincinnati Childrens Hospital
Cincinnati, Ohio 45229

More Details

NCT ID: NCT05039619
Status: Recruiting
Sponsor: Hoffmann-La Roche

Study Contact

Reference Study ID Number: WA42985 https://forpatients.roche.com/
888-662-6728 (U.S. and Canada)
global.rochegenentechtrials@roche.com