Celldex Therapeutics announced positive results from its Phase 2 clinical trial of barzolvolimab, a humanized monoclonal antibody, in patients with cold urticaria (ColdU) and symptomatic dermographism (SD), two common forms of chronic inducible urticaria (CIndU). 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. According to Dr. 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.
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 using TempTest® for ColdU and FricTest® for SD. Key results include:
-
Primary Endpoint: Significant differences were observed in the percentage of patients with a negative provocation test compared to placebo.
- Cold Urticaria:
- 150 mg q4w: 46.9% (p=0.0023)
- 300 mg q8w: 53.1% (p=0.0011)
- Placebo: 12.5%
- Symptomatic Dermographism:
- 150 mg q4w: 57.6% (p<0.0001)
- 300 mg q8w: 42.4% (p=0.0003)
- Placebo: 3.2%
- Cold Urticaria:
-
Secondary Endpoints: All secondary endpoints were also achieved at Week 12, supporting the primary endpoint results. These included responder analyses, improvements in Critical Temperature and Critical Friction Thresholds (CFT), changes in WI-NRSprovo (itch associated with provocation test), and Urticaria Control Test (UCT) scores.
- Improvements in Critical Temperature Threshold (ColdU):
- 150 mg q4w: -8.82°C (p<0.0001)
- 300 mg q8w: -9.61°C (p<0.0001)
- Placebo: -0.30°C
- Improvements in Critical Friction Threshold (Symptomatic Dermographism):
- 150 mg q4w: -2.46 pins (p<0.0001)
- 300 mg q8w: -2.27 pins (p=0.0002)
- Placebo: -0.82 pins
- Improvements in Critical Temperature Threshold (ColdU):
-
Urticaria Control Test (UCT >12):
- Cold Urticaria:
- 150 mg q4w: 58.6% (p=0.0048)
- 300 mg q8w: 68.8% (p<0.0001)
- Placebo: 31.0%
- Symptomatic Dermographism:
- 150 mg q4w: 54.8% (p=0.0015)
- 300 mg q8w: 65.5% (p<0.0001)
- Placebo: 32.0%
- Cold Urticaria:
Safety and Tolerability
Barzolvolimab was well-tolerated, with a favorable 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%), which are mechanism-related (KIT) and expected to be reversible. The rate of infections was similar between barzolvolimab-treated patients and placebo, with no association between neutropenia and infections.
Next Steps
Celldex plans to advance barzolvolimab into Phase 3 development in inducible urticaria in 2025. This follows the successful Phase 2 trial, which demonstrated clinically meaningful improvements in trigger thresholds, enabling patients to regain control of their lives.
About Chronic Inducible Urticaria
Chronic inducible urticaria (CIndU) is characterized by hives or wheals triggered by specific stimuli. ColdU involves itching, burning wheals, and angioedema upon exposure to cold temperatures, while SD involves wheals in response to scratching or rubbing of the skin. Approximately 0.5% of the population suffers from CIndU. Mast cell activation, leading to the release of soluble mediators, is believed to drive the condition. Current treatments are limited to antihistamines and trigger avoidance.
