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
- Conditions
- Lupus Nephritis
- Interventions
- Drug: PlaceboDrug: Acetaminophen/paracetamol
- Registration Number
- NCT05039619
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Diphenhydramine hydrochloride (HCl) Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Placebo Placebo Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Placebo Acetaminophen/paracetamol Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Open-Label Obinutuzumab Diphenhydramine hydrochloride (HCl) Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52. Blinded Obinutuzumab Mycophenolate Mofetil 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). Open-Label Obinutuzumab 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. Open-Label Obinutuzumab Methylprednisolone Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52. Blinded Obinutuzumab Acetaminophen/paracetamol 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). Blinded Obinutuzumab Diphenhydramine hydrochloride (HCl) 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). Placebo Methylprednisolone Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Open-Label Obinutuzumab Acetaminophen/paracetamol Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52. Blinded Obinutuzumab 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). Blinded Obinutuzumab Methylprednisolone 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). Blinded Obinutuzumab Prednisone 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). Placebo Mycophenolate Mofetil Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Placebo Prednisone Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52. Open-Label Obinutuzumab Mycophenolate Mofetil Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52. Open-Label Obinutuzumab Prednisone Younger participants aged 5 to \<12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
- Primary Outcome Measures
Name Time Method Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP) Week 76 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 eventsPercentage of Participants with Adverse Events (PP) Baseline to Week 76
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Anti-drug Antibodies (ADA) (AP) Weeks 0, 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 UPCR (AP) Baseline to Week 76 Change in eGFR (AP) Baseline 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 C4 Complement Levels (AP) Baseline to Week 76 Serum Concentrations of Obinutuzumab (AP) Baseline to 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 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 eventsTime to Onset of CRR over the Course of 76 weeks (AP) Up to Week 76 Percentage of Participants Achieving a CRR (AP) Weeks 24 and 52 Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP) Week 76 Change in C3 Complement Levels (AP) Baseline to Week 76 Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP) Baseline to Week 76 Percentage of Participants Achieving a CRR (PP) Week 76 Percentage of Participants Achieving an Overall Response (PP) Week 76 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 eventsPercentage 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 Percentage of Participants Achieving B-cell Depletion (AP) Baseline, Weeks 4, 24, 52 and 76 Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP) Baseline to Week 76 Percentage of Participants with ADAs (PP) Weeks 0, 24, 52 and 76 Change in anti-dsDNA titers (PP) Baseline to Week 76 Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP) Weeks 24, 52 and 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
Trial Locations
- Locations (42)
Panaroma Medical Center
🇿🇦Panorama, South Africa
Loma Linda University health
🇺🇸Loma Linda, California, United States
University of California San Francisco
🇺🇸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
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Texas Arthritis Center
🇺🇸El Paso, Texas, United States
Ser Servicos Especializados Em Reumatologia
🇧🇷Salvador, Bahia, Brazil
Centro de Pesquisa São Lucas
🇧🇷Campinas, São Paulo, Brazil
Universidade Federal de Sao Paulo - UNIFES
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital das Clinicas - FMUSP
🇧🇷Sao Paulo, 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
CHU de Toulouse - Hôpital des Enfants
🇫🇷Toulouse, France
Ospedale Pediatrico Bambino Gesu
🇮🇹Roma, Lazio, Italy
IRCCS G. Gaslini
🇮🇹Genova, Liguria, Italy
Clinica Pediatrica II De Marchi
🇮🇹Milano, Lombardia, Italy
CREA Hospital Mexico Americano
🇲🇽Guadalajara, Jalisco, Mexico
Clinstile S.A de C.V.
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Hospital Universitario Dr. Jose Eleuterio Gonzalez
🇲🇽Monterrey, Nuevo LEON, Mexico
Instituto de Ginecología y Reproducción
🇵🇪Lima, Peru
Clinica El Golf
🇵🇪San Isidro, Peru
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Szpital Specjalistyczny dla Dzieci i Doroslych
🇵🇱Torun, Poland
Saint-Petersburg State
🇷🇺St-peterburg, Sankt Petersburg, Russian Federation
Red Cross War Memorial Children?s Hospital
🇿🇦Cape Town, South Africa
Groote Schuur Hospital
🇿🇦Cape Town, South Africa
Hospital Sant Joan De Deu
🇪🇸Esplugas DE Llobregat, Barcelona, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital de La Paz
🇪🇸Madrid, Spain
Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica
🇪🇸Valencia, Spain
Royal Hospital For Children
🇬🇧Glasgow, United Kingdom
Alder Hey Childrens Hospital
🇬🇧Liverpool, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom