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Background: Primary Sjögren's Syndrome (pSS) is an auto-immune disease characterized by lymphocytic infiltration of the salivary and lachrymal glands leading to xerostomia and xerophthalmia, systemic features and reduced quality of life. The medical need remains unmet. S95011 is a humanized immunoglobulin G4 monoclonal antibody that specifically blocks the binding of Interleukin 7 (IL-7) to its receptor (IL-7R). IL-7 regulates T cell homeostasis, proliferation and survival for both memory and naïve T cell subsets. The involvement of T lymphocytes in the pathophysiology of pSS and the elevated levels of IL-7 and IL-7R in the blood and tissues of pSS patients, provide a rationale for investigating the therapeutic potential of S95011 in pSS patients. Objectives: This double-blind, randomized, placebo-controlled phase 2a study aimed to evaluate the preliminary therapeutic efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of multiple intravenous infusions of S95011 in patients with pSS recruited in 19 sites across Europe, US and Australia. Methods: Patients aged 18-75 years with a diagnosis of pSS, based on 2016 American College of Rheumatology (ACR) - European League Against Rheumatism (EULAR) criteria and with at least moderate systemic disease activity (EULAR SS Disease Activity Index (ESSDAI) ≥ 6 from seven domains) were eligible. Patients were randomly assigned in a 2:1 ratio to receive intravenous infusions of either 750 mg of S95011 or placebo at weeks 0, 2, 4, 7 and 10. Randomization was stratified on baseline intake of oral corticosteroids and antimalarials. The primary outcome was the change in ESSDAI from baseline to week 13 in all randomized patients. Secondary efficacy endpoints included EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Schirmer's test, Ocular Staining Score, salivary flow rate, physician and patient global assessment, assessment of fatigue and quality of life. Safety was assessed in all patients who received at least one dose of study drug up to week 28. Results: A total of 48 patients (mean (SD) age, 53.7 (12.4) years; 42 females (87.5%)) were randomized to the study with 31 patients in the S95011 group and 17 patients in the placebo group. Baseline characteristics were comparable between the two groups: Mean (SD) ESSDAI was 11.5 (3.7) and 13.1 (7.2) and mean (SD) ESSPRI was 7.1 (1.6) and 6.9 (1.7) for S95011 and placebo groups, respectively. Target engagement and exposure to the study drug achieved expected levels. The change from baseline to week 13 in ESSDAI (mean (SD)) was similar in both groups: -3.9 (4.4) for the placebo group and -3.9 (6.5) for the S95011 group. There were no statistically or clinically relevant between-group differences in ESSPRI (mean (SD)): -1.6 (2.1) in placebo group versus -1.3 (2.6) in S95011 group nor in any other endpoints, including analyses of immunoglobulins, autoantibodies and chemokines. S95011 was well-tolerated. Conclusion: S95011, an anti-IL-7 receptor monoclonal antibody, did not demonstrate efficacy in patients with pSS, suggesting that inhibition of the IL-7 pathway over 13 weeks may not be sufficient to impact disease progression. The safety profile of S95011 was acceptable. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Benjamin Fisher Consultant for: Novartis, Roche, Janssen, BMS, Servier, Galapagos, UCB, Sanofi, Financial grants from: Janssen, Servier, Galapagos, Celgene, Antónia Szántó: None declared, Maureen Rischmueller Speaker for: Abbvie, Boehringer Ingelheim, Novartis, Pfizer, UCB, Consultant for: Abbvie, Amgen, Janssen, Eli Lilly, Novartis, Pfizer, Recordati Rare Diseases, Tunde Varga: None declared, Arnd Kleyer Speaker for: Eli Lilly, Novartis, UCB, Abbvie, Amgen, Galpagos, Consultant for: Eli Lilly, Novartis, UCB, Abbvie, Amgen, Galpagos, Financial grants from: Eli Lilly, Novartis, BMS, Stephanie Finzel Speaker for: Abbvie, AstraZeneca, Chugai, Galapagos, Novartis, UCB, Consultant for: AstraZeneca, Novartis, NovoNordisk, Juan Antonio Garcia Meijide: None declared, Juan Sánchez-Bursón: None declared, Stéphanie Galtier Employed by Servier, Christine Sandré Employed by: Servier, Consultant for: Servier, Xavier Mariette Consultant for: BMS, Galapagos, GSK, Novartis, Pfizer, Servier.
Fisher et al. (Sat,) studied this question.