Celldex Therapeutics announced positive results from its Phase 2 clinical trial of barzolvolimab in patients with chronic inducible urticaria (CIndU), specifically cold urticaria (ColdU) and symptomatic dermographism (SD). The study, which included patients symptomatic despite antihistamine treatment, demonstrated that barzolvolimab met all primary and secondary endpoints with high statistical significance.
The data were presented at the American College of Allergy, Asthma & Immunology's Annual Scientific Meeting by Dr. Jonathan Bernstein.
Key Findings from the Phase 2 Trial
The Phase 2 trial (NCT05405660) randomized 196 patients with CIndU refractory to antihistamines to receive either 150 mg of barzolvolimab every 4 weeks, 300 mg every 8 weeks, or placebo. The primary endpoint was the percentage of patients with a negative provocation test at Week 12, assessed by TempTest® for ColdU and FricTest® for SD. Key secondary endpoints included improvements in Critical Temperature Threshold (CTT), Critical Friction Threshold (CFT), changes in WI-NRSprovo (itch associated with provocation test), and Urticaria Control Test (UCT) scores.
In ColdU, 46.9% and 53.1% of patients receiving 150 mg q4w and 300 mg q8w of barzolvolimab, respectively, achieved a negative provocation test (complete response) compared to 12.5% in the placebo group (p=0.0023 and p=0.0011, respectively). In SD, 57.6% and 42.4% of patients receiving 150 mg q4w and 300 mg q8w of barzolvolimab, respectively, achieved a negative provocation test compared to 3.2% in the placebo group (p<0.0001 and p=0.0003, respectively).
Significant improvements were also observed in secondary endpoints. For example, patients with ColdU experienced improvements in CTT of -8.82°C (p<0.0001) and -9.61°C (p<0.0001) in the 150 mg q4w and 300 mg q8w groups, respectively, compared to -0.30°C in the placebo group. Patients with SD experienced improvements in CFT of -2.46 pins (p<0.0001) and -2.27 pins (p=0.0002) in the 150 mg q4w and 300 mg q8w groups, respectively, compared to -0.82 pins in the placebo group.
Safety and Tolerability
Barzolvolimab was well-tolerated, with a safety profile consistent with prior studies. Most adverse events were grade 1 (mild). The most common treatment-emergent adverse events in barzolvolimab-treated patients were hair color changes (13%) and neutropenia (10%), both mechanism-related and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo, with no association between neutropenia and infections.
Clinical Significance
"Chronic inducible urticaria is a devastating disease for patients who despite constant vigilance often find it impossible to avoid their disease triggers and are impacted by severe itching and burning hives that dramatically impact all aspects of their lives," said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "Barzolvolimab is the first drug to achieve success in a large, randomized, placebo-controlled study in chronic inducible urticaria and we are excited to report that all primary and secondary endpoints across the study were highly statistically significant and clinically meaningful."
Next Steps
Celldex plans to advance barzolvolimab into Phase 3 development in inducible urticaria in 2025.
