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Trial record 1 of 1 for:    obinutuzumab lupus
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A Study to Evaluate the Safety and Efficacy of Obinutuzumab Compared With Placebo in Participants With Lupus Nephritis (LN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02550652
First received: September 14, 2015
Last updated: March 13, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Lupus Nephritis
Drug: Mycophenolate Mofetil/Mycophenolic Acid
Drug: Obinutuzumab
Other: Placebo
Drug: Methylprednisolone
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Proportion of Participants who Achieve Protocol Defined Complete Renal Response (CRR) [ Time Frame: Week 52 ]

Secondary Outcome Measures:
  • Proportion of Participants who Achieve Protocol Defined Overall Response [ Time Frame: Week 52 ]
  • Time to First Protocol Defined Overall Response Over the Course of 52 Weeks [ Time Frame: From Baseline (Day 1) to Week 52 ]
  • Proportion of Participants who Achieve Protocol Defined Partial Renal Response (PRR) [ Time Frame: Week 52 ]
  • Proportion of Participants who Achieve Protocol Defined CRR [ Time Frame: Week 24 ]
  • Time to Protocol Defined CRR Over the Course of 52 Weeks [ Time Frame: From Baseline (Day 1) to Week 52 ]
  • Percent Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels [ Time Frame: Baseline, Week 104 ]
  • Percent Change From Baseline in C3 Levels [ Time Frame: Baseline, Week 104 ]
  • Percent Change From Baseline in C4 Levels [ Time Frame: Baseline, Week 104 ]
  • Proportion of Participants who Achieve Protocol Defined Modified CRR (mCRR1) [ Time Frame: Week 52 ]
  • Proportion of Participants who Achieve Protocol Defined Second mCRR (mCRR2) [ Time Frame: Week 52 ]
  • Proportion of Participants who Achieve Protocol Defined Third mCRR (mCRR3) [ Time Frame: Week 52 ]
  • Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score [ Time Frame: Baseline (Day 1), Weeks 4, 12, 24, 36, 52/early termination ]
  • Change From Baseline in Circulating CD19-Positive B-Cell Levels [ Time Frame: Baseline, Week 104 ]
  • Percentage of Participants With Adverse Events [ Time Frame: From Baseline up to Week 104 ]
  • Circulating T-Cell Levels [ Time Frame: Baseline (Day 1), Weeks 2, 4, 12, 24, 36, 52, 76, 104 ]
  • Circulating Neutrophil Levels [ Time Frame: Baseline (Day 1), Weeks 2, 4, 12, 24, 36, 52, 76, 104 ]
  • Percentage of Participants With Positive Antibody Titers to Mumps, Rubella, Varicella, Tetanus, Influenza, and Streptococcus pneumoniae [ Time Frame: Weeks 24, 52/early termination ]
  • Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab [ Time Frame: Baseline (Day 1), Weeks 24, 52, 76, 104 ]
  • Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab [ Time Frame: Pre-infusion (within 30 minutes [min] prior to start of infusion), end of infusion (infusion duration: 255 min for first dose and 195 min for subsequent doses) on Days 1, 15, 168, 182; Days 28, 84, 252, 364, 532, 728 ]
  • Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab [ Time Frame: Pre-infusion (within 30 min prior to start of infusion), end of infusion (infusion duration: 255 min for first dose and 195 min for subsequent doses) on Days 1, 15, 168, 182; Days 28, 84, 252, 364, 532, 728 ]
  • Systemic Clearance of Obinutuzumab [ Time Frame: Pre-infusion (within 30 min prior to start of infusion), end of infusion (infusion duration: 255 min for first dose and 195 min for subsequent doses) on Days 1, 15, 168, 182; Days 28, 84, 252, 364, 532, 728 ]
  • Volume of Distribution Under Steady State (Vss) of Obinutuzumab [ Time Frame: Pre-infusion (within 30 min prior to start of infusion), end of infusion (infusion duration: 255 min for first dose and 195 min for subsequent doses) on Days 1, 15, 168, 182; Days 28, 84, 252, 364, 532, 728 ]
  • Terminal Plasma Half-Life (t1/2) of Obinutuzumab [ Time Frame: Pre-infusion (within 30 min prior to start of infusion), end of infusion (infusion duration: 255 min for first dose and 195 min for subsequent doses) on Days 1, 15, 168, 182; Days 28, 84, 252, 364, 532, 728 ]

Estimated Enrollment: 120
Actual Study Start Date: November 30, 2015
Estimated Study Completion Date: August 29, 2020
Estimated Primary Completion Date: August 29, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Obinutuzumab
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 based on tolerability 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.
Drug: Mycophenolate Mofetil/Mycophenolic Acid
MMF/MPA will be administered as per schedule specified in the respective arm.
Drug: Obinutuzumab
Obinutuzumab will be administered as per schedule specified in the respective arm.
Other Name: Gazyva, GA101, RO5072759
Drug: Methylprednisolone
Methylprednisolone IV will be administered as per schedule specified in the respective arm.
Drug: Prednisone
Prednisone will be administered as per schedule specified in the respective arm.
Placebo Comparator: Placebo
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 based on tolerability 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.
Drug: Mycophenolate Mofetil/Mycophenolic Acid
MMF/MPA will be administered as per schedule specified in the respective arm.
Other: Placebo
Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.
Drug: Methylprednisolone
Methylprednisolone IV will be administered as per schedule specified in the respective arm.
Drug: Prednisone
Prednisone will be administered as per schedule specified in the respective arm.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02550652

Contacts
Contact: Reference Study ID Number: WA29748 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 77 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02550652     History of Changes
Other Study ID Numbers: WA29748
2015-002022-39 ( EudraCT Number )
Study First Received: September 14, 2015
Last Updated: March 13, 2017

Additional relevant MeSH terms:
Lupus Nephritis
Lupus Erythematosus, Systemic
Obinutuzumab
Nephritis
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Mycophenolic Acid
Mycophenolate mofetil
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 21, 2017