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 (POSTERITY)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Obinutuzumab; Drug: Mycophenolate Mofetil; Drug: Acetaminophen/paracetamol; Drug: Diphenhydramine hydrochloride (HCl); Drug: Methylprednisolone; Drug: Prednisone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 40150-150
      • Recruiting
      • Ser Servicos Especializados Em Reumatologia
  • SP
    • Sao Paulo, SP, Brazil, 04026-000
      • Active, not recruiting
      • Universidade Federal de Sao Paulo - UNIFES
    • Sao Paulo, SP, Brazil, 05403-010
      • Recruiting
      • Hospital das Clinicas - FMUSP
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • The Hospital for Sick Children
• France
  • Le Kremlin Bicêtre, France, 94275
    • Recruiting
    • CH de Bicêtre; Pediatrie Generale
  • Paris, France, 75019
    • Recruiting
    • Hôpital Robert Debré; Nephrologie pediatrique
  • Paris, France, 75743
    • Recruiting
    • Hop Necker Enfants Malades;UIH
  • Toulouse, France, 31000
    • Recruiting
    • CHU de Toulouse - Hôpital des Enfants; Nephro - Rhumato - Medecine Interne - Hypertension
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00165
      • Recruiting
      • Ospedale Pediatrico Bambino Gesu; U.O. Di Nefrologia E Dialisi
  • Liguria
    • Genova, Liguria, Italy, 16148
      • Recruiting
      • IRCCS G. Gaslini; U.O. Nefrologia, Dialisi e Trapianto
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Recruiting
      • Clinica Pediatrica II De Marchi
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44620
      • Recruiting
      • CREA Hospital Mexico Americano; Clinica Pediatrica de Reumatologia y Enfermedades Autoinmunes
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • Recruiting
      • Clinstile S.A de C.V.
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Recruiting
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez; Pediatria
• Peru
  • Lima, Peru
    • Recruiting
    • Instituto de Ginecología y Reproducción
  • San Isidro, Peru, L27 Lima
    • Recruiting
    • Clínica El Golf
• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne; Klinika Chorob Nerek i Nadci?nienia Dzieci i Mlodziezy
  • Torun, Poland, 87-100
    • Recruiting
    • Szpital Specjalistyczny dla Dzieci i Doroslych; Oddzial Kliniczny Pediatrii i Nefrologii
• Russian Federation
  • Sankt Petersburg
    • St-peterburg, Sankt Petersburg, Russian Federation, 194100
      • Suspended
      • Saint-Petersburg State; Pediatrics Medical Academy
• South Africa
  • Cape Town, South Africa, 7925
    • Recruiting
    • Groote Schuur Hospital; Renal Unit
  • Cape Town, South Africa, 7700
    • Recruiting
    • Red Cross War Memorial Children?s Hospital; Nephrology Unit
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal ; Servicio de Reumatologia
  • Madrid, Spain, 28046
    • Active, not recruiting
    • Hospital de La Paz; Unidad de Reumatologia Pediatrica
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica
  • Barcelona
    • Esplugas DE Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Withdrawn
    • Royal Hospital for Children
  • Liverpool, United Kingdom, L12 2AP
    • Recruiting
    • Alder Hey Childrens Hospital
  • London, United Kingdom, WC1N 3JH
    • Active, not recruiting
    • Great Ormond Street Hospital for Children
• United States
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University Health
    • San Francisco, California, United States, 94117
      • Recruiting
      • University of California San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Active, not recruiting
      • Children's Hospital Colorado, Anchutz Medical Campus
  • Georgia
    • Atlanta, Georgia, United States, 20010
      • Recruiting
      • Emory Children's Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University Health University Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Recruiting
      • Louisiana State University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
  • New York
    • Queens, New York, United States, 11042
      • Recruiting
      • Cohen Children's Medical Center of New York; Pediatrics
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Childrens Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Chldren's Hospital of Philadelphia
  • Texas
    • El Paso, Texas, United States, 79902
      • Recruiting
      • Texas Arthritis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo participants will receive obinutuzumab matched placebo 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.; Drug: Placebo; Placebo matching obinutuzumab will be administered by IV on Day 1, Day 14, Week 24, Week 26 and Week 52.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	Weeks 24, 52, and 76
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)	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	Week 76
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2022
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 13, 2029

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 14, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antipyretics; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Immunological; Dermatologic Agents; Anti-Bacterial Agents; Hypnotics and Sedatives; Anesthetics, Local; Antibiotics, Antineoplastic; Anti-Allergic Agents; Antitubercular Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Antibiotics, Antitubercular; Methylprednisolone; Acetaminophen; Diphenhydramine; Promethazine; Prednisone; Mycophenolic Acid; Obinutuzumab
• Other Study ID Numbers: WA42985; 2021-000097-29 (EudraCT Number); 2023-505825-15-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No