Phase 2b randomized trial of OX40 inhibitor telazorlimab for moderate-to-severe atopic dermatitis

Abstract

Background: Telazorlimab is a humanized anti-OX40 monoclonal antibody being studied for treatment of T-cell-mediated diseases.

Objective: This randomized, placebo-controlled, phase 2b dose-range finding study investigated efficacy, safety, pharmacokinetics, and immunogenicity of telazorlimab in subjects with atopic dermatitis.

Methods: In this 2-part study (NCT03568162), adults (≥18 years) with moderate-to-severe disease were randomized to various regimens of subcutaneous telazorlimab or placebo for 16 weeks' blinded treatment, followed by 38 weeks' open-label treatment and 12 weeks' drug-free follow-up. Telazorlimab treatment groups (following a loading dose) in part 1 were 300 mg every 2 weeks; 300 mg every 4 weeks; or 75 mg every 4 weeks. Part 2 evaluated telazorlimab 600 mg every 2 weeks. The primary end point was percentage change from baseline in Eczema Area and Severity Index (EASI) at week 16. Safety assessments included incidence of treatment-emergent adverse events.

Results: The study randomized 313 subjects in part 1 and 149 in part 2. At 16 weeks, the least squares mean percentage change from baseline in EASI was significantly greater in subjects receiving telazorlimab 300 mg every 2 weeks (part 1) and 600 mg every 2 weeks (part 2) versus placebo (-54.4% vs -34.2% for part 1 and -59.0% vs -41.8% for part 2, P = .008 for both). Telazorlimab was well tolerated, with similar distribution of adverse events between telazorlimab- and placebo-treated subjects in both part 1 and part 2.

Conclusion: Telazorlimab, administered subcutaneously at 300 mg every 2 weeks or 600 mg every 2 weeks following a loading dose, was well tolerated and induced significant and progressive clinical improvement in adults with moderate-to-severe atopic dermatitis.

Keywords: Atopic dermatitis; anti-OX40 receptor; humanized monoclonal antibody; phase 2; telazorlimab.

Fig 1

Study design. q2w, Every 2 weeks; q4w, every 4 weeks.

Fig 2

Disposition of patients during blinded treatment phase. q2w, Every 2 weeks; q4w, every 4 weeks.

Fig 3

Time course of response as measured by change from baseline in EASI. Statistical comparison at week 16 only. ∗P < .05 at week 16 for telazorlimab 300 mg q2w versus placebo in part 1 and for telazorlimab 600 mg q2w versus placebo in part 2. q2w, Every 2 weeks; q4w, every 4 weeks.