A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis
Phase 3
Active, not recruiting
- 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
Inclusion Criteria
- 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
Exclusion Criteria
- 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)
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
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Hopital Bichat Claude Bernard
🇫🇷Paris, France
Hopital Rangueil
🇫🇷Toulouse, France
Städtisches Klinik Dresden-Friedrichstadt
🇩🇪Dresden, Germany
Universitätsklinikum "Carl Gustav Carus"
🇩🇪Dresden, Germany
Scroll for more (63 remaining)NYU Langone Medical Center🇺🇸New York, New York, United States