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

NCT05039619 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: WA429852021-000097-292023-505825-15-00
• Study Type: interventional
• Target: 40
• Locations: 12 countries
• Sites: 42

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.

Conditions

Lupus Nephritis

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)

  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

  Week 76

• Percentage of Participants with Adverse Events (PP)

  Baseline to Week 76

Secondary Outcomes (26)

• 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

• Change in UPCR (AP)

  Baseline to Week 76

Study Arms (3)

Blinded Obinutuzumab

EXPERIMENTAL

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; Drug: Mycophenolate Mofetil; Drug: Acetaminophen/paracetamol; Drug: Diphenhydramine hydrochloride (HCl); Drug: Methylprednisolone; Drug: Prednisone

Placebo

PLACEBO COMPARATOR

Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.

Drug: Placebo; Drug: Mycophenolate Mofetil; Drug: Acetaminophen/paracetamol; Drug: Diphenhydramine hydrochloride (HCl); Drug: Methylprednisolone; Drug: Prednisone

Open-Label Obinutuzumab

EXPERIMENTAL

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; Drug: Mycophenolate Mofetil; Drug: Acetaminophen/paracetamol; Drug: Diphenhydramine hydrochloride (HCl); Drug: Methylprednisolone; Drug: Prednisone

Interventions

Obinutuzumab DRUG

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.

Also known as: Gazyva

Blinded Obinutuzumab; Open-Label Obinutuzumab

Placebo DRUG

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

Placebo

Mycophenolate Mofetil DRUG

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.

Blinded Obinutuzumab; Open-Label Obinutuzumab; Placebo

Acetaminophen/paracetamol DRUG

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

Blinded Obinutuzumab; Open-Label Obinutuzumab; Placebo

Diphenhydramine hydrochloride (HCl) DRUG

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

Blinded Obinutuzumab; Open-Label Obinutuzumab; Placebo

Methylprednisolone DRUG

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

Blinded Obinutuzumab; Open-Label Obinutuzumab; Placebo

Prednisone DRUG

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.

Blinded Obinutuzumab; Open-Label Obinutuzumab; Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Genentech, Inc.: collaborator

Study Sites (42)

Loma Linda University health

Loma Linda, California, 92354, United States

RECRUITING

UCSF Benioff Childrens Hospital

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado, Anchutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Emory Children's Center

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

Louisiana State University

Shreveport, Louisiana, 71103, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Cohen Children's Medical Center of New York

Queens, New York, 11042, United States

RECRUITING

Cincinnati Childrens Hospital

Cincinnati, Ohio, 45229, United States

RECRUITING

Chldren?s Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

WITHDRAWN

Texas Arthritis Center

El Paso, Texas, 79902, United States

WITHDRAWN

Ser Servicos Especializados Em Reumatologia

Salvador, Estado de Bahia, 40150-150, Brazil

RECRUITING

Centro de Pesquisa São Lucas

Campinas, São Paulo, 13060-904, Brazil

RECRUITING

Hospital das Clinicas - FMUSP

São Paulo, São Paulo, 05403-000, Brazil

RECRUITING

Universidade Federal de Sao Paulo - UNIFES

São Paulo, 04024-002, Brazil

ACTIVE NOT RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

Hospital Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

CH de Bicêtre

Le Kremlin-Bicêtre, 94275, France

RECRUITING

Hôpital Robert Debré

Paris, 75019, France

RECRUITING

Hop Necker Enfants Malades

Paris, 75743, France

RECRUITING

CHU de Toulouse - Hôpital des Enfants

Toulouse, 31000, France

RECRUITING

Ospedale Pediatrico Bambino Gesu

Rome, Lazio, 00165, Italy

RECRUITING

IRCCS G. Gaslini

Genoa, Liguria, 16148, Italy

RECRUITING

Clinica Pediatrica II De Marchi

Milan, Lombardy, 20122, Italy

RECRUITING

CREA Hospital Mexico Americano

Guadalajara, Jalisco, 44620, Mexico

RECRUITING

Clinstile S.A de C.V.

Mexico City, Mexico CITY (federal District), 06700, Mexico

RECRUITING

Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo León, 64460, Mexico

RECRUITING

Instituto de Ginecología y Reproducción

Lima, Peru

ACTIVE NOT RECRUITING

Clinica El Golf

San Isidro, L27 Lima, Peru

ACTIVE NOT RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-294, Poland

RECRUITING

Szpital Specjalistyczny dla Dzieci i Doroslych

Torun, 87-100, Poland

WITHDRAWN

Saint-Petersburg State

St-peterburg, Sankt-Peterburg, 194100, Russia

WITHDRAWN

Red Cross War Memorial Children?s Hospital

Cape Town, 7700, South Africa

WITHDRAWN

Groote Schuur Hospital

Cape Town, 7925, South Africa

WITHDRAWN

Panaroma Medical Center

Panorama, 7500, South Africa

RECRUITING

Hospital Sant Joan De Deu

Esplugas de Llobregat, Barcelona, 08950, Spain

RECRUITING

Hospital Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital de La Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, 46026, Spain

RECRUITING

Royal Hospital For Children

Glasgow, G51 4TF, United Kingdom

WITHDRAWN

Alder Hey Childrens Hospital

Liverpool, L12 2AP, United Kingdom

RECRUITING

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

RECRUITING

Related Publications (1)

• Dossier C, Bonneric S, Baudouin V, Kwon T, Prim B, Cambier A, Couderc A, Moreau C, Deschenes G, Hogan J. Obinutuzumab in Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome in Children. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1555-1562. doi: 10.2215/CJN.0000000000000288. Epub 2023 Sep 6.

  PMID: 37678236 DERIVED

MeSH Terms

Conditions

Lupus Nephritis

Interventions

obinutuzumab; Mycophenolic Acid; Acetaminophen; Diphenhydramine; Methylprednisolone; Prednisone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: WA42985 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. and Canada); global.rochegenentechtrials@roche.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: September 9, 2021
• Study Start: May 12, 2022
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 14, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

US (11); BR (4); FR (4); ZA (3); ME (3); IT (3); ES (4); PL (2); RU (1); CA (2); PE (2); GB (3)