Positive efficacy and favorable safety of barzolvolimab in chronic inducible urticaria: phase II trial results

Abstract

Background

Chronic inducible urticaria (CIndU) is characterized by mast cell-mediated wheals elicited in response to definite triggers. Barzolvolimab (monoclonal anti-KIT antibody) specifically inhibits the activation of KIT by stem cell factors, which control the survival and activity of mast cells. We reported efficacy and safety through 12W from a phase II study on patients with CIndU refractory to antihistamines (NCT05405660).

Methods

This ongoing, double-blind, placebo-controlled trial randomized patients with cold urticaria (ColdU) and symptomatic dermographism (SD) to receive barzolvolimab subcutaneous at 150 mg every 4 weeks, 300 mg every 8 weeks, or placebo during a 20W placebo-controlled period with 24W follow-up. The primary endpoint was the percentage of patients with negative provocation tests (ColdU: TempTest < 4°C, SD: FricTest: 0 pins) at 12W. Secondary endpoints included the Worst Itch Numeric Rating Scale and safety.

Results

A total of 196 patients enrolled: 97 with ColdU and 99 with SD. Mean baseline provocation thresholds for TempTest ranged from 18.6°C to 20.7°C and 3.55 to 3.64 pins for FricTest. At 12W, the percentage of patients with negative TempTest was 46.9% (P = .0023), 53.1% (P = .0011), and 12.5%, and negative FricTest was 57.6% (P < .0001), 42.2% (P = .0003), and 3.2% for 150 mg every 4 weeks, 300 mg every 8 weeks and placebo, respectively. Barzolvolimab was well-tolerated with hair color changes with grade I to II neutropenia being the most common adverse events.

Conclusion

The study met the primary endpoint with unprecedented, clinically meaningful, and statistically significant complete response rates (negative provocation test) in patients with ColdU and SD at 12W. This phase II barzolvolimab study is the first large, randomized placebo-controlled study to achieve a successful outcome for CIndU and supports advancing to phase III registrational studies.