Inhibition of CD40L with Frexalimab in Multiple Sclerosis.

Background: The CD40-CD40L costimulatory pathway regulates adaptive and innate immune responses and has been implicated in the pathogenesis of multiple sclerosis. Frexalimab is a second-generation anti-CD40L monoclonal antibody being evaluated for the treatment of multiple sclerosis.

Methods: In this phase 2, double-blind, randomized trial, we assigned, in a 4:4:1:1 ratio, participants with relapsing multiple sclerosis to receive 1200 mg of frexalimab administered intravenously every 4 weeks (with an 1800-mg loading dose), 300 mg of frexalimab administered subcutaneously every 2 weeks (with a 600-mg loading dose), or the matching placebos for each active treatment.

An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy.

Background And Aims: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP.

Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study.

The objective of this study was to assess the effect of secukinumab, a monoclonal antibody that inhibits interleukin (IL)-17A, on number of new active brain magnetic resonance imaging (MRI) lesions in subjects with relapsing-remitting multiple sclerosis (MS). Subjects (N = 73) were randomized 1:1 to secukinumab 10 mg/kg or placebo by intravenous infusion at weeks 0, 2, 4, 8, 12, 16, and 20. MRI scans were obtained within 30 days prior to randomization, on a monthly basis during the treatment period, and at study completion.

Characterization of dose-response for count data using a generalized MCP-Mod approach in an adaptive dose-ranging trial.

Understanding the dose-response relationship is a key objective in Phase II clinical development. Yet, designing a dose-ranging trial is a challenging task, as it requires identifying the therapeutic window and the shape of the dose-response curve for a new drug on the basis of a limited number of doses. Adaptive designs have been proposed as a solution to improve both quality and efficiency of Phase II trials as they give the possibility to select the dose to be tested as the trial goes.

Distribution of a calcium channel subunit in dystrophic axons in multiple sclerosis and experimental autoimmune encephalomyelitis.

Multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) are immune-mediated diseases of the CNS. They are characterized by widespread inflammation, demyelination and a variable degree of axonal loss. Recent magnetic resonance spectroscopy studies have indicated that axonal damage and loss are a reliable correlate of permanent clinical disability.