Abstract: FR-OR136
A Phase 2 Randomized, Controlled Study of Obinutuzumab with Mycophenolate and Corticosteroids in Proliferative Lupus Nephritis
Session Information
- High-Impact Clinical Trials
November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
Abstract Time: 03:15 PM - 03:30 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
- Aroca Martinez, Gustavo, Universidad Simon Bolivar / Clinica de la Costa, Barranquilla, Colombia
- Alvarez, Analia, CEMIC, Buenos Aries, Argentina
- Fragoso loyo, Hilda Esther, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
- Zuta, Adolfina Elizabeth, Instituto de Ginecologia y Reproduccion, Lima, Peru
- Furie, Richard, Northwell Health, Great Neck, New York, United States
- Brunetta, Paul Gardner, Genentech, Inc., South San Francisco, California, United States
- Schindler, Thomas, F. Hoffmann-La Roche AG, Basel, Switzerland
- Hassan, Imran, Hoffmann-La Roche Limited, Mississauga, Ontario, Canada
- Cascino, Matthew, Genentech, Inc., South San Francisco, California, United States
- Garg, Jay P., Genentech, Inc., South San Francisco, California, United States
- Malvar, Ana, Organizacion Maedica de Investigacion, Buenos Aires, Argentina
Background
Type I anti-CD20 antibodies such as rituximab fail to achieve complete B-cell depletion in lupus nephritis (LN). NOBILITY tested whether enhanced B-cell depletion with the type II anti-CD20, obinutuzumab (OBI), could improve responses in LN compared to placebo (PBO). (NCT02550652)
Methods
Patients with active Class III/IV LN (n=125) received standard-of-care mycophenolate and steroids and were randomized to OBI or PBO and followed for 104 weeks. The primary endpoint (EP) was complete renal response (CRR) at week 52. Key secondary EPs included overall renal response (ORR) and modified CRR (mCRR). Results through week 76 are reported. The two-sided alpha level was 0.2.
Results
Baseline mean urine protein:creatinine ratio (UPCR) and serum creatinine were 3.1 g/g and 0.84 mg/dL. OBI was associated with increased renal responses vs. PBO at weeks 52 and 76 (Table). 80% of OBI pts and 0% of PBO pts had CD19+ count <0.441 cells/μL at week 52. Significant improvements in anti-dsDNA, C3, and C4 were observed with OBI vs. PBO. Through week 76, serious adverse events (OBI 24% vs. PBO 29%) and serious infections (6% vs. 18%) were not increased with OBI. Nonserious infusion-related reactions were more common with OBI (16% vs. 10%). There were 5 deaths (1 OBI, 4 PBO).
Conclusion
NOBILITY met its primary and secondary efficacy EPs. OBI was superior to PBO for the achievement of renal response at 12 and 18 months in proliferative LN patients treated with mycophenolate and steroids. There were no unexpected safety findings.
Table. Outcomes at Weeks 52 and 76
Funding
- Commercial Support – F. Hoffmann-La Roche