A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Registration Number
- NCT04221477
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 271
- Diagnosis of active or active/chronic ISN/RPS 2003 Class III or IV proliferative LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
- Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour collection
- Other inclusion criteria may apply
Key
- Pregnancy or breastfeeding
- Severe renal impairment or the need for dialysis or renal transplantation
- Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
- Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
- Known active infection of any kind or recent major episode of infection
- Intolerance or contraindication to study therapies
- Other exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab MMF Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab Obinutuzumab Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab Prednisone Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab Methylprednisolone Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab Acetaminophen Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Obinutuzumab Diphenhydramine Participants will be randomized into 2 groups. Group 1 will receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Group 2 receive obinutuzumab 1000 mg IV at baseline and Weeks 2, 24, 26, and 52 plus MMF and oral prednisone. Group 2 participants will receive a placebo infusion at their Week 50 visit. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo Obinutuzumab Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo MMF Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo Prednisone Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo Acetaminophen Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo Diphenhydramine Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80. Placebo Methylprednisolone Placebo participants will receive obinutuzumab matched placebo at baseline and Weeks 2, 24, 26, 50, and 52 plus MMF and oral prednisone. Participants with an adequate response at Week 76 will continue receiving blinded obinutuzumab infusions every 6 months starting at Week 80. Participants without an adequate response at Week 76 may be eligible for open-label obinutuzumab starting at Week 80.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Complete Renal Response (CRR) At Week 76
- Secondary Outcome Measures
Name Time Method Time to Onset of CRR From baseline to Week 76 Change in Fatigue (FACIT-F) Scale From baseline to Week 76 Percentage of Participants who Achieve Complete Renal Response (CRR) with Successful Prednisone Taper at Week 76 At Week 76 Percentage of Participants who Achieve a Proteinuric Response At Week 76 Change in Systematic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) From baseline to Week 76 Percentage of Participants who Achieve CRR with Serum Creatinine Criteria At Week 76 Percentage of Participants who Achieve an Overall Renal Response (ORR), Defined as Achievement of Either CRR or Partial Renal Response (PRR) At Week 50 Percentage of Participants who Experience Death or Renal-related Events From baseline to Week 76 Mean Change in Estimated Glomerular Filtration Rate (eGFR) From baseline to Week 76 Maximum Serum Concentration of Obinutuzumab Baseline, Week 2, 4, 12, 26, 36, 50, 52, 64, 76 and early study discontinuation Change in Anti-dsDNA Titer From baseline to Week 50 Change in Complement C3 From baseline to Week 50 Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 From baseline to Week 76 Percentage of Participants with Adverse Events of Special Interest (Infusion Related Reactions, Neutropenia, Infections, Thrombocytopenia) From baseline to Week 76 Percentage of Participants with Anti-Drug Antibodies (ADAs) at Baseline and ADAs Post-Treatment From baseline to Week 76 Change from Baseline in Total Peripheral B-Cell Count Baseline, Week 4, 12, 24, 50 and 76
Trial Locations
- Locations (73)
A.O. Spedali Civili Di Brescia-P.O. Spedali Civili
🇮🇹Brescia, Lombardia, Italy
Clínica San Juan Bautista CSJB
🇵🇪Lima, Peru
NYU Langone Medical Center
🇺🇸New York, New York, United States
University of Utah Health Science center
🇺🇸Salt Lake City, Utah, United States
Hospital das Clinicas - FMUSP Ribeirao Preto
🇧🇷Ribeirao Preto, São Paulo, Brazil
Hopital Henri Mondor
🇫🇷Creteil, France
Hopital Claude Huriez
🇫🇷Lille, France
Universitaetsmedizin Johannes Gutenberg
🇩🇪Mainz, Germany
Hospital Universitario
🇲🇽Monterrey, Nuevo LEON, Mexico
Ortopedyczno Rehab Szpital Klinic im Wiktora Degi UM
🇵🇱Poznan, Poland
Szpital Kliniczny Dzieciatka Jezus
🇵🇱Warszawa, Poland
Federal Centre of Heart, Blood and Endocrinology n.a. V.A.Almazov
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
?Kazan (Privolzhsky) Federal University?
🇷🇺Kazan, Tatarstan, Russian Federation
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
University of Alabama at Birmingham Medical Center
🇺🇸Birmingham, Alabama, United States
Wallace Rheumatic Study Center
🇺🇸Beverly Hills, California, United States
Kaiser Permanente - Fontana
🇺🇸Fontana, California, United States
Kaiser Permanente - San Francisco Medical Center
🇺🇸San Francisco, California, United States
Univ Colorado Health Sci Ctr
🇺🇸Aurora, Colorado, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
AD-CARE, University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Oklahoma Medical Research Foundation
🇺🇸Oklahoma City, Oklahoma, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
Sanatorio Allende
🇦🇷Cordoba, Argentina
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Hopital Rangueil
🇫🇷Toulouse, France
Universitätsklinikum "Carl Gustav Carus"
🇩🇪Dresden, Germany
Universitätskrankenhaus Tübingen
🇩🇪Tübingen, Germany
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Policlinico di Bari
🇮🇹Bari, Puglia, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Veneto, Italy
Hospital Nacional Cayetano Heredia
🇵🇪San Martin de Porres, Peru
Uniwersytecki Szpital Kliniczny nr 4 w Lublinie
🇵🇱Lublin, Poland
Medyczne Centrum Hetmanska
🇵🇱Poznan, Poland
Städtisches Klinik Dresden-Friedrichstadt
🇩🇪Dresden, Germany
Groote Schuur Hospital and University of Cape Town
🇿🇦Cape Town, South Africa
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Stanford University Medical Center
🇺🇸Stanford, California, United States
Georgia Nephrology
🇺🇸Lawrenceville, Georgia, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Southwest Rheumatology
🇺🇸Mesquite, Texas, United States
Organizacion Medica de Investigacion
🇦🇷Buenos Aires, Argentina
DOM Centro de Reumatología
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Ser Servicos Especializados Em Reumatologia
🇧🇷Salvador, Bahia, Brazil
Instituto Pro-Renal
🇧🇷Curitiba, Paraná, Brazil
Centro Multidisciplinar de Estudos Clínicos - CEMEC*X*
🇧🇷Santo Andre, São Paulo, Brazil
Clinica De La Costa
🇨🇴Barranquilla, Colombia
Hospital Universitario San Ignacio
🇨🇴Bogota, Colombia
Hospital Pablo Tobon Uribe
🇨🇴Medellin, Colombia
Charité Campus Mitte, Med.Klinik, Rheumatologie und Klinische Immunologie
🇩🇪Berlin, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Meir Medical Center
🇮🇱Kfar- Saba, Israel
Rabin MC- Belinson campus
🇮🇱Petach Tikva, Israel
Azienda Ospedaliera Universitaria Careggi
🇮🇹Firenze, Toscana, Italy
Rheuma Medicus Zaklad Opieki Zdrowotnej
🇵🇱Warszawa, Poland
Hospital das Clinicas - FMUSP
🇧🇷Sao Paulo, São Paulo, Brazil
Sourasky Medical Centre
🇮🇱Tel-Aviv, Israel
Ospedale Policlinico San Martino
🇮🇹Genova, Liguria, Italy
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Centro de Investigación y Tratamiento Reumatológico S.C.
🇲🇽Mexico, DF, Mexico CITY (federal District), Mexico
Instituto Peruano del Hueso y la Articulación
🇵🇪Lima, Peru
Instituto del Cerebro y la Columna Vertebral SAC
🇵🇪Lima, Peru
Instituto de Ginecología y Reproducción
🇵🇪Lima, Peru
Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. Prof. Eleonory Reicher
🇵🇱Warszawa, Poland
Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wroclaw, Poland
Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
SBEI HPE "The First St.Petersburg State Medical University n.a. acad. I.P.Pavlova"of MoH of RF
🇷🇺Sankt-peterburg, Sankt Petersburg, Russian Federation