Clinical trial NCT05039619: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Lupus Nephritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2021-09-09
Enrollment: 40
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)
timeFrame: Week 76
measure: Percentage of Participants with Adverse Events (PP)
timeFrame: Baseline to Week 76
Secondary outcomes:
measure: Percentage of Participants Achieving a CRR (AP)
timeFrame: Weeks 24 and 52
measure: Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP)
timeFrame: Week 76
measure: Percentage of Participants who Achieve a PRR (AP)
timeFrame: Week 76
measure: Percentage of Participants Achieving an Overall Response (CRR or PRR) (AP)
timeFrame: Weeks 24, 52, and 76
measure: Change in UPCR (AP)
timeFrame: Baseline to Week 76
measure: Change in eGFR (AP)
timeFrame: Baseline to Week 76
measure: Time to Onset of CRR over the Course of 76 weeks (AP)
timeFrame: Up to Week 76
measure: Percentage of Participants who Experience Treatment Failure (AP)
timeFrame: Week 12 to Week 76
measure: Change in anti-dsDNA titers (AP)
timeFrame: Baseline to Week 76
measure: Change in C3 Complement Levels (AP)
timeFrame: Baseline to Week 76
measure: Change in C4 Complement Levels (AP)
timeFrame: Baseline to Week 76
measure: Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP)
timeFrame: Baseline to Week 76
measure: Serum Concentrations of Obinutuzumab (AP)
timeFrame: Baseline to Week 76
measure: Percentage of Participants Achieving B-cell Depletion (AP)
timeFrame: Baseline, Weeks 4, 24, 52 and 76
measure: Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP)
timeFrame: Baseline to Week 76
measure: Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP)
timeFrame: Baseline to Week 76
measure: Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP)
timeFrame: Baseline to Week 76
measure: Percentage of Participants with Anti-drug Antibodies (ADA) (AP)
timeFrame: Weeks 0, 24, 52 and 76
measure: Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP)
timeFrame: Weeks 24, 52 and 76
measure: Percentage of Participants Achieving a CRR (PP)
timeFrame: Week 76
measure: Percentage of Participants Achieving an Overall Response (PP)
timeFrame: Week 76
measure: Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP)
timeFrame: Week 76
measure: Change in eGFR (PP)
timeFrame: Baseline to Week 76
measure: Percentage of Participants Achieving B-cell Depletion (PP)
timeFrame: Baseline, Weeks 4, 24, 52 and 76
measure: Percentage of Participants with ADAs (PP)
timeFrame: Weeks 0, 24, 52 and 76
measure: Change in anti-dsDNA titers (PP)
timeFrame: Baseline to Week 76
Other outcomes:
Locations:
city: Loma Linda
country: United States
facility: Loma Linda University health
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado, Anchutz Medical Campus
state: Colorado
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Queens
country: United States
facility: Cohen Children's Medical Center of New York
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Chldren?s Hospital of Philadelphia
state: Pennsylvania
city: El Paso
country: United States
facility: Texas Arthritis Center
state: Texas
city: Salvador
country: Brazil
facility: Ser Servicos Especializados Em Reumatologia
state: Bahia
city: Campinas
country: Brazil
facility: Centro de Pesquisa São Lucas
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFES
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas - FMUSP
state: São Paulo
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Hospital Sainte-Justine
state: Quebec
city: Le Kremlin Bicêtre
country: France
facility: CH de Bicêtre
city: Paris
country: France
facility: Hôpital Robert Debré
city: Paris
country: France
facility: Hop Necker Enfants Malades
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital des Enfants
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
state: Lazio
city: Genova
country: Italy
facility: IRCCS G. Gaslini
state: Liguria
city: Milano
country: Italy
facility: Clinica Pediatrica II De Marchi
state: Lombardia
city: Guadalajara
country: Mexico
facility: CREA Hospital Mexico Americano
state: Jalisco
city: Mexico City
country: Mexico
facility: Clinstile S.A de C.V.
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo LEON
city: Lima
country: Peru
facility: Instituto de Ginecología y Reproducción
city: San Isidro
country: Peru
facility: Clinica El Golf
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Torun
country: Poland
facility: Szpital Specjalistyczny dla Dzieci i Doroslych
city: St-peterburg
country: Russian Federation
facility: Saint-Petersburg State
state: Sankt Petersburg
city: Cape Town
country: South Africa
facility: Red Cross War Memorial Children?s Hospital
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Panorama
country: South Africa
facility: Panaroma Medical Center
city: Esplugas DE Llobregat
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital de La Paz
city: Valencia
country: Spain
facility: Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica
city: Glasgow
country: United Kingdom
facility: Royal Hospital For Children
city: Liverpool
country: United Kingdom
facility: Alder Hey Childrens Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: