A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants.

Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab.

A Randomized Phase I Study of the Anti-Interleukin-33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease.

Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)-33. IL-33 is a broad-acting epithelial "alarmin" cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first-in-human, phase I, randomized, double-blind, placebo-controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) of tozorakimab.

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.

Background: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).

Methods: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19.

A CD40L-targeting protein reduces autoantibodies and improves disease activity in patients with autoimmunity.

The CD40/CD40L axis plays a central role in the generation of humoral immune responses and is an attractive target for treating autoimmune diseases in the clinic. Here, we report the generation and clinical results of a CD40L binding protein, VIB4920, which lacks an Fc domain, therefore avoiding platelet-related safety issues observed with earlier monoclonal antibody therapeutics that targeted CD40L. VIB4920 blocked downstream CD40 signaling events, resulting in inhibition of human B cell activation and plasma cell differentiation, and did not induce platelet aggregation in preclinical studies.

Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb.

Background: IL-13 has an important role in atopic dermatitis (AD) pathogenesis. Tralokinumab is a fully human mAb that potently and specifically neutralizes IL-13.

Objective: We sought to evaluate the efficacy and safety of tralokinumab in adults with moderate-to-severe AD.

Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo- and active-controlled clinical trials.

GSK372475 is a triple reuptake inhibitor with approximately equipotent inhibition of serotonin, norepinephrine, and dopamine transporters. Two randomized, placebo- and active-controlled, double-blind studies examined the efficacy and safety of GSK372475 in outpatients (aged 18-64 years) with a diagnosis of major depressive episode associated with major depressive disorder (MDD). Patients were randomized 1:1:1 to placebo, GSK372475 (1-2 mg/d), or active control (Study 1: venlafaxine XR 150-225 mg/d; Study 2: paroxetine 20-30 mg/d).