A proof-of-concept study showed an investigational drug was safe and effective for patients with primary Sjögren syndrome.
“CD40–CD154-mediated T cell–B cell interactions in primary Sjögren syndrome contribute to aberrant lymphocyte activation in inflamed tissue, leading to sialadenitis and other tissue injury,” the researchers said. They investigated the safety and efficacy of iscalimab, a novel anti-CD40 monoclonal antibody, among participants with primary Sjögren syndrome.
The study included 10 investigational sites across Europe and the United States. Participants were randomized 2:1 to iscalimab or placebo in cohort 1 or cohort 2. In cohort 1, 12 participants received subcutaneous iscalimab at a dose of 3 mg per kg or placebo at weeks 0, 2, 4, and 8. In cohort 2, 32 participants received intravenous iscalimab at a dose of 10 mg per kg or placebo at weeks 0, 2, 4, and 8. At week 12, participants in both cohorts received open-label iscalimab, with the same dose and route, for 12 weeks.
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Primary outcomes included the safety, tolerability, and efficacy of isaclimab, measured by the change in European League Against Rheumatism Sjögren syndrome disease activity index (ESSDAI) score after 12 weeks of treatment.
The researchers found intravenous treatment with iscalimab was associated with a mean reduction of 5.21 points (95% CI, 0.96-9.46) in ESSDAI scores compared with placebo. However, they did not observe any significant differences in ESSDAI scores between subcutaneous iscalimab and placebo.
For adverse events, the researchers observed similar rates between the treatment and placebo groups in cohort 1. In cohort 2, adverse events occurred in 52% and 64% of participants in the iscalimab and placebo groups, respectively.
While 2 serious adverse events were reported, they were not found to be related to treatment with iscalimab, the researchers said. These included 1 case of bacterial conjunctivitis in cohort 1 and 1 case of atrial fibrillation in cohort 2.
“To our knowledge, this is the first randomized, placebo-controlled proof-of-concept study of a new investigational drug for primary Sjögren syndrome that indicates preliminary efficacy,” the researchers concluded. “Our data suggest a role of CD40–CD154 interactions in primary Sjögren syndrome pathology, and the therapeutic potential for CD40 blockade in this disease should be investigated further.”
Fisher BA, SzantoA, Ng WF, et al. Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study [published online January 23, 2020]. Lancet Rheumatol. doi:10.1016/S2665-9913(19)30135-3