Objectives To evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren’s syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study.
Methods Patients with pSS, EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) ≥6, were randomised to ianalumab single infusion at either 3 mg/kg (n=6), 10 mg/kg (n=12) or placebo (n=9). Outcomes were measured blinded at baseline and weeks 6, 12, 24, and unblinded at end of study (EoS) when B cell numbers had recovered. Clinical outcomes included ESSDAI, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), salivary flow rate, ocular staining score, physician global assessment and patient assessments of fatigue and general quality of life. Laboratory-based measures included circulating leucocyte subsets and markers of B cell activity.
Results A similar trend showing positive therapeutic effect by ianalumab was observed across the primary clinical outcome (ESSDAI) and all secondary clinical outcomes (ESSPRI, Multidimensional Fatigue Inventory, Short Form-36, global assessments by physician and patient) versus the placebo-treated group. Rapid and profound B cell depletion of long-lasting duration occurred after a single infusion of ianalumab at either dose. Serum Ig light chains decreased, with return to baseline levels at EoS. Changes in some clinical outcomes persisted through to EoS in the higher dose group. Adverse effects were largely limited to mild to moderate infusion reactions within 24 hours of ianalumab administration.
Conclusions Overall results in this single-dose study suggest potent and sustained B cell depletion by ianalumab could provide therapeutic benefits in patients with pSS without major side effects.
- B cells
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TD and MGP contributed equally.
Handling editor Josef S Smolen
Presented at Portions of these reported findings have been presented in poster or podium format at the following conferences: (1) Poster presentation at the European Union League Against Rheumatism 2016 Congress: Dörner T, Posch M, Wagner F, Hüser A, Fischer T, Mooney L, Petricoul O, Maguire P, Pal P, Doucet J, Cabanski M, Kamphausen E, Oliver S. Double-blind, randomized study of VAY736 single dose treatment in patients with primary Sjögren’s syndrome (pSS). Ann Rheum Dis 2016; 75(suppl 2):S300. (2) Podium presentation at the American College of Rheumatology 2016 National Meeting: Dörner T, Posch M, Wagner F, Hüser A, Fischer T, Mooney L, Petricoul O, Maguire P, Pal P, Doucet J, Cabanski M, Kamphausen E, Kazma R, Oliver S. Safety and efficacy of single dose VAY736 (anti-BAFFR mAb) in patients with primary Sjögren’s syndrome (pSS). Arthritis Rheum 2016; 68 (suppl S10):3033.
Contributors SJO, OP, MAV, TD, MGP, LM, FDW and AH participated in the design, conduct and analysis of the study. HG provided preclinical background and participated in analysis and manuscript preparation. MC, JMM, MGP and CS participated in the conduct and analysis of the study. All authors contributed to manuscript preparation and review.
Funding This study was funded by Novartis Pharma.
Competing interests All authors listed as affiliated with Novartis Pharma are full-time employees of the company, with SJO, OP, LM, MAV and CS also owning company stock. TD has received scientific consulting fees from Novartis. FDW, MGP and AH are employees of the Charité Research Organisation which has past and currently ongoing contract work with Novartis Pharma.
Patient consent for publication Not required.
Ethics approval This study was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Guidelines for Good Clinical Practice and local regulations. The protocol, consent form and any other written information provided to patients were approved by the Ethik-Kommission des Landesamt für Gesundheit und Soziales Berlin.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Additional study design details and study results are available on www.clinicaltrials.gov under the listed trial identifier.