A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obinutuzumab in Participants With Systemic Lupus Erythematosus

Author(s):

Edward M. Vital,¹ Zahir Amoura,² Stella Botha,³ Maria A. D'Agostino,⁴ Sunil Kumar,⁵ Fedra I. Palazuelos,⁶ Grzegorz Rozumek,⁷ Adolfina E. Zuta Santillán,⁸ Viviane A. Souza,⁹ Biruh Workeneh,¹⁰ Justine Maller,¹¹ Oliver Meier,¹² Jay P. Garg,¹¹ Richard A. Furie¹³ 

Leeds Institute of Rheumatology and Musculoskeletal Medicine, University of Leeds, Leeds, UK; 2.  French National Reference Center for SLE, Pitié Salpêtrière, Paris, France; 3.  Winelands Medical Research Centre, Cape Town, South Africa; 4.  Policlinico Universitario Agostino Gemelli, Rome, Italy; 5.  Middlemore Hospital, Auckland, New Zealand; 6.  Centro de Investigación y Tratamiento Reumatológico S.C., Mexico City, Mexico; 7.  REUMATOP Grzegorz Rozumek, Karin Pistorius Spółka Jawna, Wrocław, Poland; 8.  Instituto de Ginecología y Reproducción, Lima, Peru; 9.  Centro Mineiro de Pesquisa – CMIP, Juiz de Fora, Brazil; 10. Prolato Clinical Research Center, Houston, TX, USA; 11. Genentech, Inc., South San Francisco, CA, USA; 12.  F. HoffmannLa Roche Ltd, Basel, Switzerland; 13. Division of Rheumatology, Northwell Health, Great Neck, NY, USA

Author Disclosures: 

E.M. Vital has received consulting fees from AbbVie, AstraZeneca, Eli Lilly and Company, F. Hoffmann-La Roche Ltd/Genentech, Inc., Merck, Novartis, Otsuka, Pfizer and UCB. 
Z. Amoura has received research support and consulting fees from Amgen, AstraZeneca, Genentech, Inc., GlaxoSmithKline, Kezar and Novartis. 
S. Botha, S. Kumar, G. Rozumek, A.E. Zuta Santillán, V.A. Souza and B. Workeneh have nothing to disclose. 
M.A. D’Agostino has received speaker and consulting fees from AbbVie, Alfasigma Global, Amgen, AstraZeneca, BMS, Eli Lilly, Galapagos, GlaxoSmithKline, J&J, MSD, Novartis, J&J Sanofi and UCB. 
F.I. Palazuelos has received research support and consulting fees from AbbVie, Amgen Inc. Eli Lilly, F. Hoffmann-La Roche Ltd, Novartis and UCB. 
J. Maller and J.P. Garg are employees of Genentech, Inc., and shareholders of F. HoffmannLa Roche Ltd. 
O. Meier is an employee and shareholder of F. Hoffmann-La Roche Ltd. 
R.A. Furie has received research support and consulting fees from Chugai Pharmaceutical Co., Ltd., F. Hoffmann-La Roche Ltd, Genentech, Inc. and GlaxoSmithKline; is a consultant for AstraZeneca, EMD Serono, Novartis, Biogen, and BMS; is an investigator for AstraZeneca, Novartis, Biogen, BMS, and Kyverna; and is a speaker for AstraZeneca.

Abstract or description:

Objectives: B cells are key drivers of systemic lupus erythematosus (SLE) pathogenesis. Obinutuzumab, a glycoengineered type II anti-CD20 antibody, demonstrated superiority versus placebo in the Phase III REGENCY study (NCT04221477) in participants with lupus nephritis, when added to standard therapy (ST). The ALLEGORY (NCT04963296) study evaluates the efficacy, safety, pharmacokinetics and pharmacodynamics of obinutuzumab versus placebo in participants with SLE, when added to ST. 

Methods: Participants with SLE and high disease activity (SLEDAI-2K ≥8 and BILAG-2004 Category A severity in ≥1 domain and/or Category B severity in ≥2 domains), receiving ST (immunosuppressants, antimalarials and/or glucocorticoids), are randomized 1:1 to receive blinded infusions of obinutuzumab (1000 mg) or placebo at Week (W) 0, W2, W24 and W26. After completing blinded treatment at W52, eligible participants from both groups may enter an 18-month open-label treatment phase, where they receive obinutuzumab at W54, W56, W78 and W104. The primary endpoint is the difference between the proportions of obinutuzumabtreated versus placebo-treated participants achieving SLE Responder Index-4 (SRI-4) at W52 (≥4 points SLEDAI-2K reduction, <1 new BILAG A or <2 new BILAG B items and no worsening of ≥0.3 points on a 3-point Physician’s Global Assessment-Visual Analogue Scale). Secondary endpoints include the proportions of participants who achieve BILAG-based Composite Lupus Assessment or SRI-6 at W52, sustained glucocorticoid control (W40-W52) for those on ≥10 mg/day prednisone (or equivalent) at baseline, sustained SRI-4 response (W40-W52) and the time to first BILAG flare over 52 weeks. 

Results: ALLEGORY is fully enrolled with 303 participants from 64 sites across 14 countries, distributed across Latin America (54.1%), eastern Europe (14.9%), North America (12.2%), western Europe (9.2%), Africa (8.9%) and Asia–Pacific (0.7%). The median (range) age of participants is 41.0 (18-70) years and 90.4% are female. 

Conclusions: Full results of the ALLEGORY study will be available upon study completion. 

Additional abstract information Acknowledgements: 

We thank all trial participants, the staff and the trial investigators. This trial was funded by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Nucleus Global and funded by F. Hoffmann-La Roche Ltd.