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A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)

Primary Purpose

Lupus Nephritis

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Mycophenolate Mofetil/Mycophenolic Acid
Obinutuzumab
Placebo
Methylprednisolone
Prednisone
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Univ of California, San Diego
  • Stanford University Medical Center
  • Emory Uni ; Division of Rheumatology
  • Suny Downstate Medical Center; Rheumatology
  • North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology
  • Columbia University Medical Center
  • Ohio State University; Division of Nephrology
  • Cemic; Haematology
  • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
  • Organizacion Medica de Investigacion
  • Ser Servicos Especializados Em Reumatologia
  • Hospital das Clinicas - UFMG
  • Centro Mineiro de Pesquisa - CMIP
  • Instituto Scribner.
  • LMK Serviços Médicos S/S
  • Universidade Federal de Sao Paulo - UNIFES
  • Clinica De La Costa
  • Hospital Universitario San Ignacio
  • Riesgo De Fractura; Rheumatology
  • Hospital Pablo Tobon Uribe
  • Hospital Clinica Catolica
  • HOPITAL HENRI MONDOR; SERVICE DE Nephrologie
  • Hopital Claude Huriez; Internal Medicine
  • Hopital europeen Marseille; Service de medecine interne
  • Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii
  • Hopital Bichat Claude Bernard; Nephrologie
  • Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique
  • Rambam Medical Center; Rheumatology
  • Beilinson Medical Center; Rheumatology
  • Sheba Medical Center; Tel Hashomer
  • Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare
  • Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia
  • Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
  • Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
  • Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
  • Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
  • Hospital General De Mexico; Rheumatology
  • Centro de Investigación Clínica de Morelia S.C.
  • Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
  • Trial Labs
  • Instituto de Ginecología y Reproducción
  • Centro de Investigación Delgado; Clinica Delgado
  • Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
  • Hospital Nacional Cayetano Heredia; Rheumatology
  • Hospital Clinic i Provincial; Servicio de Nefrologia
  • Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Obinutuzumab

Placebo

Arm Description

Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52
Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.

Secondary Outcome Measures

Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52
OR includes both CRR and partial renal response (PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of <1.0. 2. If baseline protein:creatinine ratio is > 3.0, then urine protein:creatinine ratio of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF.
Percentage of Participants With First Protocol Defined Overall Response Over the Course of 52 Weeks
OR includes both CRR and partial renal response(PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in upcr, with one of these conditions met: 1. If baseline upcr is ≤3.0, then upcr of <1.0. 2. If baseline pcr is > 3.0, then upcr of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF. Percentage of participants with response at various time points were measured using Kaplan Meier method.
Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52
PRR defined as serum creatinine ≤15% above baseline value, no urinary red cell casts and either RBCs/HPF ≤ 50% above baseline or < 10 RBCs/HPF, 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then a urine protein:creatinine ratio of < 1.0. 2. If baseline protein:creatinine ratio is > 3.0, then a urine protein:creatinine ratio of < 3.0.
Percentage of Participants Who Achieve Protocol Defined CRR at Week 24
CRR defined as normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Percentage of Participants With First Protocol Defined CRR Over the Course of 52 Weeks
CRR included normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the ULN range of central laboratory values if baseline serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values. Percentage of participants with response at various time points were measured using Kaplan Meier method.
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52
Anti-dsDNA antibodies are a group of anti-nuclear antibodies targeting double stranded DNA.
Change From Baseline in Complement Component 3 (C3) Levels at Week 52
Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Change From Baseline in C4 Levels at Week 52
Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52
mCRR1 has got two components only, i.e. serum Creatinine and urinary protein to creatinine ratio. mCRR1 is defined by attainment of normalization of serum creatinine as evidenced by 1.) serum creatinine ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine ≤ the ULN range of central laboratory values and 2.) Urinary protein to creatinine ratio <0.5.
Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52
mCRR2 is defined by normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts), and urinary protein to creatinine ratio <0.5. Normalization of serum creatinine as evidenced by the following: Serum creatinine ≤15% above baseline if baseline (Day 1) serum creatinine is above the normal range of the central laboratory values or ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52
mCRR3 is defined by normalization of serum creatine as evidenced by serum creatinine ≤ the ULN range of central laboratory values and urinary protein to creatinine ratio < 0.5.
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs), Infections and Serious infections.
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia
Infusion related reaction is defined as any event reported within 24 hours of infusion and thought to be causally related to the investigational agent by the investigator. Grade 3 or higher infections include all events of Grade 3 to 5 under the SOC of infections and infestations. Drug-related neutropenia is defined as events in the Roche AE Grouped Term (AEGT) "Neutropenia and associated complications" and thought to be causally related to the investigational agent by the investigator. Drug-related thrombocytopenia is defined as events in the Standard MedDRA Query (SMQ) "Haematopoietic Thrombocytopenia narrow" and thought to be causally related to the investigational agent by the investigator.
Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab
Antibodies are a blood protein produced in response to and counteracting a specific antigen.
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels
CD19+ B cell is a B-lymphocyte with a transmembrane protein that is encoded by the gene CD19.
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab
Systemic Clearance of Obinutuzumab
Volume of Distribution Under Steady State (Vss) of Obinutuzumab
Terminal Plasma Half-Life (t1/2) of Obinutuzumab
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score
Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.

Full Information

First Posted
September 14, 2015
Last Updated
July 27, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02550652
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 13, 2015 (Actual)
Primary Completion Date
January 15, 2019 (Actual)
Study Completion Date
October 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
126 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Obinutuzumab
Arm Type
Experimental
Arm Description
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 750-1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil/Mycophenolic Acid
Intervention Description
MMF/MPA will be administered as per schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
Gazyva, GA101, RO5072759
Intervention Description
Obinutuzumab will be administered as per schedule specified in the respective arm.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
Methylprednisolone IV will be administered as per schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone will be administered as per schedule specified in the respective arm.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieve Protocol Defined Complete Renal Response (CRR) at Week 52
Description
Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Time Frame
From baseline to Week 52
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieve Protocol Defined Overall Response (OR) at Week 52
Description
OR includes both CRR and partial renal response (PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of <1.0. 2. If baseline protein:creatinine ratio is > 3.0, then urine protein:creatinine ratio of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF.
Time Frame
From baseline to Week 52
Title
Percentage of Participants With First Protocol Defined Overall Response Over the Course of 52 Weeks
Description
OR includes both CRR and partial renal response(PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in upcr, with one of these conditions met: 1. If baseline upcr is ≤3.0, then upcr of <1.0. 2. If baseline pcr is > 3.0, then upcr of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF. Percentage of participants with response at various time points were measured using Kaplan Meier method.
Time Frame
From baseline to Week 52
Title
Percentage of Participants Who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52
Description
PRR defined as serum creatinine ≤15% above baseline value, no urinary red cell casts and either RBCs/HPF ≤ 50% above baseline or < 10 RBCs/HPF, 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then a urine protein:creatinine ratio of < 1.0. 2. If baseline protein:creatinine ratio is > 3.0, then a urine protein:creatinine ratio of < 3.0.
Time Frame
From baseline to Week 52
Title
Percentage of Participants Who Achieve Protocol Defined CRR at Week 24
Description
CRR defined as normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Time Frame
Week 24
Title
Percentage of Participants With First Protocol Defined CRR Over the Course of 52 Weeks
Description
CRR included normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the ULN range of central laboratory values if baseline serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values. Percentage of participants with response at various time points were measured using Kaplan Meier method.
Time Frame
From Baseline to Week 52
Title
Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Antibody Levels at Week 52
Description
Anti-dsDNA antibodies are a group of anti-nuclear antibodies targeting double stranded DNA.
Time Frame
Baseline and Week 52
Title
Change From Baseline in Complement Component 3 (C3) Levels at Week 52
Description
Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Time Frame
Baseline and Week 52
Title
Change From Baseline in C4 Levels at Week 52
Description
Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
Time Frame
Baseline, Week 52
Title
Percentage of Participants Who Achieve Protocol Defined Modified CRR (mCRR1) at Week 52
Description
mCRR1 has got two components only, i.e. serum Creatinine and urinary protein to creatinine ratio. mCRR1 is defined by attainment of normalization of serum creatinine as evidenced by 1.) serum creatinine ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine ≤ the ULN range of central laboratory values and 2.) Urinary protein to creatinine ratio <0.5.
Time Frame
Week 52
Title
Percentage of Participants Who Achieve Protocol Defined Second mCRR (mCRR2) at Week 52
Description
mCRR2 is defined by normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts), and urinary protein to creatinine ratio <0.5. Normalization of serum creatinine as evidenced by the following: Serum creatinine ≤15% above baseline if baseline (Day 1) serum creatinine is above the normal range of the central laboratory values or ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
Time Frame
Week 52
Title
Percentage of Participants Who Achieve Protocol Defined Third mCRR (mCRR3) at Week 52
Description
mCRR3 is defined by normalization of serum creatine as evidenced by serum creatinine ≤ the ULN range of central laboratory values and urinary protein to creatinine ratio < 0.5.
Time Frame
Week 52
Title
Percentage of Participants With Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs), Infections and Serious infections.
Time Frame
From Baseline up to Week 104
Title
Percentage of Participants With Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia
Description
Infusion related reaction is defined as any event reported within 24 hours of infusion and thought to be causally related to the investigational agent by the investigator. Grade 3 or higher infections include all events of Grade 3 to 5 under the SOC of infections and infestations. Drug-related neutropenia is defined as events in the Roche AE Grouped Term (AEGT) "Neutropenia and associated complications" and thought to be causally related to the investigational agent by the investigator. Drug-related thrombocytopenia is defined as events in the Standard MedDRA Query (SMQ) "Haematopoietic Thrombocytopenia narrow" and thought to be causally related to the investigational agent by the investigator.
Time Frame
From baseline up to Week 104
Title
Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab
Description
Antibodies are a blood protein produced in response to and counteracting a specific antigen.
Time Frame
From baseline up to Week 104
Title
Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels
Description
CD19+ B cell is a B-lymphocyte with a transmembrane protein that is encoded by the gene CD19.
Time Frame
Baseline, Week 2, Week 4, Week 12, Week 24, Week 52
Title
Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab
Time Frame
Week 0, Week 24, Week 52
Title
Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab
Time Frame
Week 0, Week 24, Week 52
Title
Systemic Clearance of Obinutuzumab
Time Frame
Day 0, Week 24, Week 52
Title
Volume of Distribution Under Steady State (Vss) of Obinutuzumab
Time Frame
Day 0, Week 24, Week 52
Title
Terminal Plasma Half-Life (t1/2) of Obinutuzumab
Time Frame
Day 0, Week 24, Week 52
Title
Change From Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score
Description
Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.
Time Frame
Baseline (Day 1), Weeks 4, 12, 24, 36, 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Univ of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Emory Uni ; Division of Rheumatology
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Suny Downstate Medical Center; Rheumatology
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
North Shore - Long Island Jewish Hospital Health System; Rheumatology & Allergy- Clinical Immunology
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Ohio State University; Division of Nephrology
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Cemic; Haematology
City
Buenos Aires
ZIP/Postal Code
C1431FWO
Country
Argentina
Facility Name
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
City
San Juan
ZIP/Postal Code
J5400DIL
Country
Argentina
Facility Name
Organizacion Medica de Investigacion
City
San Nicolás
ZIP/Postal Code
C1015ABO
Country
Argentina
Facility Name
Ser Servicos Especializados Em Reumatologia
City
Salvador
State/Province
BA
ZIP/Postal Code
40150-150
Country
Brazil
Facility Name
Hospital das Clinicas - UFMG
City
Belo Horizonte
State/Province
MG
ZIP/Postal Code
31270-901
Country
Brazil
Facility Name
Centro Mineiro de Pesquisa - CMIP
City
Juiz de Fora
State/Province
MG
ZIP/Postal Code
36010-570
Country
Brazil
Facility Name
Instituto Scribner.
City
Curitiba
State/Province
PR
ZIP/Postal Code
80440-020
Country
Brazil
Facility Name
LMK Serviços Médicos S/S
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90480-000
Country
Brazil
Facility Name
Universidade Federal de Sao Paulo - UNIFES
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04026-000
Country
Brazil
Facility Name
Clinica De La Costa
City
Barranquilla
ZIP/Postal Code
080020
Country
Colombia
Facility Name
Hospital Universitario San Ignacio
City
Bogota
ZIP/Postal Code
000472
Country
Colombia
Facility Name
Riesgo De Fractura; Rheumatology
City
Bogota
Country
Colombia
Facility Name
Hospital Pablo Tobon Uribe
City
Medellin
ZIP/Postal Code
050034
Country
Colombia
Facility Name
Hospital Clinica Catolica
City
Goicoechea
ZIP/Postal Code
10801
Country
Costa Rica
Facility Name
HOPITAL HENRI MONDOR; SERVICE DE Nephrologie
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital Claude Huriez; Internal Medicine
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital europeen Marseille; Service de medecine interne
City
Marseille
ZIP/Postal Code
13003
Country
France
Facility Name
Groupe Hospitalier Pitie-Salpetriere; Service de Medecine Interne Ii
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Hopital Bichat Claude Bernard; Nephrologie
City
Paris
ZIP/Postal Code
75877
Country
France
Facility Name
Hopital Rangueil; Service de Nephrologie & D'Immunologie Clinique
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Rambam Medical Center; Rheumatology
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Beilinson Medical Center; Rheumatology
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Sheba Medical Center; Tel Hashomer
City
Ramat Gan
ZIP/Postal Code
5262100
Country
Israel
Facility Name
Ospedale San Giovanni Bosco; entro di Ricerche di Immunopatologia e Documentazione su Malattie Rare
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10154
Country
Italy
Facility Name
Azienda Ospedaliera di Padova; Dipartimento di Medicina - UOC di Reumatologia
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
City
Mexicali
State/Province
BAJA California
ZIP/Postal Code
21100
Country
Mexico
Facility Name
Unidad de Investigacion en Enfermedades Cronico-Degenerativa; Reumatologia
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44620
Country
Mexico
Facility Name
Centro de Estudios de Investigacion Basica Y Clinica S.C.; Reumatologia
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44690
Country
Mexico
Facility Name
Instituto Nacional de Ciencias Médicas Y de La Nutricion Zubirán
City
Mexico City
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
Tlalpan 14000
Country
Mexico
Facility Name
Hospital General De Mexico; Rheumatology
City
Mexico, D.F.
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
6726
Country
Mexico
Facility Name
Centro de Investigación Clínica de Morelia S.C.
City
Morelia
State/Province
Michoacan
ZIP/Postal Code
58070
Country
Mexico
Facility Name
Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
City
Culiacán Rosales
State/Province
Sinaloa
ZIP/Postal Code
80000
Country
Mexico
Facility Name
Trial Labs
City
Panama
ZIP/Postal Code
0801
Country
Panama
Facility Name
Instituto de Ginecología y Reproducción
City
Lima
Country
Peru
Facility Name
Centro de Investigación Delgado; Clinica Delgado
City
Miraflores
ZIP/Postal Code
15074
Country
Peru
Facility Name
Centro de Investigaciones Medicas/Hospital Maria Auxiliadora
City
San Juan de Miraflores
ZIP/Postal Code
15801
Country
Peru
Facility Name
Hospital Nacional Cayetano Heredia; Rheumatology
City
San Martin de Porres
ZIP/Postal Code
15102
Country
Peru
Facility Name
Hospital Clinic i Provincial; Servicio de Nefrologia
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Regional Universitario Carlos Haya; Servicio de Reumatologia
City
Malaga
ZIP/Postal Code
29009
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study 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).
Citations:
PubMed Identifier
34615636
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.
Results Reference
derived
PubMed Identifier
33693991
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.
Results Reference
derived

Learn more about this trial

A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)

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