Clinical trial NCT02550652: A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients With ISN/RPS 2003 Class III or IV Lupus Nephritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Nephritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-15
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase II study will compare the efficacy and safety of obinutuzumab plus mycophenolate mofetil (MMF)/mycophenolic acid (MPA) with placebo plus MMF/MPA in participants with proliferative LN.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Systemic Lupus Erythematosus (SLE), according to current American College of Rheumatology (ACR) criteria
* Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months prior to or during screening. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
* Proteinuria (urine protein to creatinine ratio) greater than (\>) 1.0
* For women who are not postmenopausal (greater than or equal to \[\>/=\] 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of less than (\<) 1 percent (%) per year, during the treatment period and for at least 18 months after the last dose of study drug
* For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \<1% per year during the treatment period and for at least 12 months after the last dose of study drug and agreement to refrain from donating sperm during this same period

Exclusion Criteria:

* Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE
* Presence of rapidly progressive glomerulonephritis
* Severe renal impairment as defined by estimated Glomerular Filtration Rate (GFR) \<30 milliliters per minute (mL/min) or the need for dialysis or renal transplant
* Greater than 50% of glomeruli with sclerosis on renal biopsy
* Treatment with cyclophosphamide or calcineurin inhibitors within the 3 months prior to randomization
* Unstable disease with thrombocytopenia or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions
* History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
* Significant or uncontrolled medical disease in any organ system not related to SLE or LN, which, in the investigator's opinion, would preclude participant participation
* Concomitant chronic conditions, excluding SLE, (e.g., asthma, Crohn's disease) that required oral or systemic steroid use in the 52 weeks prior to screening
* Previous treatment with an anti-cluster of differentiation (CD20)-targeted therapy within 12 months
* Previous treatment with a biologic B-cell-targeted therapy (other than anti-CD20) within 6 months of randomization
* Known intolerance to MMF or MPA

Primary outcomes:
measure: Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52
timeFrame: From baseline to Week 52
Secondary outcomes:
measure: Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52
timeFrame: From baseline to Week 52
measure: Time to OR Over 52 Weeks
timeFrame: From baseline to Week 52
measure: Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Protocol Defined CRR at Week 24
timeFrame: Week 24
measure: Time to CRR Over 52 Weeks
timeFrame: From Baseline to Week 52
measure: Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Complement Component 3 (C3) Levels at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in C4 Levels at Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52
timeFrame: Week 52
measure: Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52
timeFrame: Week 52
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From baseline to approximately 7 years and 8 months
measure: Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia
timeFrame: From baseline to approximately 7 years and 8 months
measure: Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab
timeFrame: From baseline to approximately 7 years and 8 months
measure: Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels
timeFrame: Baseline, Week 2, Week 4, Week 12, Week 24, Week 52, Week 104, B Cell Follow-Up (Bcfu) at months 6, 12, 18, 24, 30, 36, 42 and 48
measure: Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab
timeFrame: Week 0, Week 24, Week 52
measure: Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab
timeFrame: Baseline to Week 52
measure: Systemic Clearance of Obinutuzumab
timeFrame: Day 0, Week 24, Week 52
measure: Volume of Distribution Under Steady State (Vss) of Obinutuzumab
timeFrame: Day 0, Week 24, Week 52
measure: Terminal Plasma Half-Life (t1/2) of Obinutuzumab
timeFrame: Day 0, Week 24, Week 52
measure: Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score
timeFrame: Baseline (Day 1), Weeks 4, 12, 24, 36, 52
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Univ of California, San Diego
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Atlanta
country: United States
facility: Emory Uni ; Division of Rheumatology
state: Georgia
city: Brooklyn
country: United States
facility: Suny Downstate Medical Center; Rheumatology
state: New York
city: Great Neck
country: United States
facility: North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State University; Division of Nephrology
state: Ohio
city: Buenos Aires
country: Argentina
facility: Cemic; Haematology
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
city: San Nicolás
country: Argentina
facility: Organizacion Medica de Investigacion
city: Salvador
country: Brazil
facility: Ser Servicos Especializados Em Reumatologia
state: BA
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas - UFMG
state: MG
city: Juiz de Fora
country: Brazil
facility: Centro Mineiro de Pesquisa - CMIP
state: MG
city: Curitiba
country: Brazil
facility: Instituto Scribner.
state: PR
city: Porto Alegre
country: Brazil
facility: LMK Serviços Médicos S/S
state: RS
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo - UNIFES
state: SP
city: Barranquilla
country: Colombia
facility: Clinica De La Costa
city: Bogota
country: Colombia
facility: Hospital Universitario San Ignacio
city: Bogota
country: Colombia
facility: Riesgo De Fractura; Rheumatology
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Goicoechea
country: Costa Rica
facility: Hospital Clinica Catolica
city: Creteil
country: France
facility: HOPITAL HENRI MONDOR; SERVICE DE Nephrologie
city: Lille
country: France
facility: Hopital Claude Huriez; Internal Medicine
city: Marseille
country: France
facility: Hopital europeen Marseille; Service de medecine interne
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii
city: Paris
country: France
facility: Hopital Bichat Claude Bernard; Nephrologie
city: Toulouse
country: France
facility: Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique
city: Haifa
country: Israel
facility: Rambam Medical Center; Rheumatology
city: Petach Tikva
country: Israel
facility: Beilinson Medical Center; Rheumatology
city: Ramat Gan
country: Israel
facility: Sheba Medical Center; Tel Hashomer
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare
state: Piemonte
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia
state: Veneto
city: Mexicali
country: Mexico
facility: Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
state: BAJA California
city: Guadalajara
country: Mexico
facility: Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
state: Jalisco
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
state: Jalisco
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
state: Mexico CITY (federal District)
city: Mexico, D.F.
country: Mexico
facility: Hospital General De Mexico; Rheumatology
state: Mexico CITY (federal District)
city: Morelia
country: Mexico
facility: Centro de Investigación Clínica de Morelia S.C.
state: Michoacan
city: Culiacán Rosales
country: Mexico
facility: Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
state: Sinaloa
city: Panama
country: Panama
facility: Trial Labs
city: Lima
country: Peru
facility: Instituto de Ginecología y Reproducción
city: Miraflores
country: Peru
facility: Centro de Investigación Delgado; Clinica Delgado
city: San Juan de Miraflores
country: Peru
facility: Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
city: San Martin de Porres
country: Peru
facility: Hospital Nacional Cayetano Heredia; Rheumatology
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial; Servicio de Nefrologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, Fragoso-Loyo H, Zuta-Santillan E, Schindler T, Brunetta P, Looney CM, Hassan I, Malvar A. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 Jan;81(1):100-107. doi: 10.1136/annrheumdis-2021-220920. Epub 2021 Oct 6.
citation: Dossier C, Hogan J. Response to Majeranowski. Pediatr Nephrol. 2021 Jun;36(6):1653. doi: 10.1007/s00467-021-04982-4. Epub 2021 Mar 10. No abstract available.