A Phase 3 Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria (CSU)

This is a global, multicenter, randomized, double-blind, parallel group, placebo-controlled phase 3 study investigating the efficacy, safety and tolerability of barzolvolimab in adult participants with Chronic Spontaneous Urticaria (CSU) who are symptomatic despite treatment with non-sedating second generation H1-antihistamines at 1-4 times the locally approved dose.

There is a screening period of up to 4 weeks, followed by a 24-week placebo-controlled treatment period, a 28-week active treatment period where all participants receive barzolvolimab followed by a 16-week treatment free period.

Approximately 915 adult participants (610 in the active arms and 305 in the placebo arm) will be randomly assigned to the treatment arms.

Primary Outcome Measures

1. Mean change from baseline to Week 12 of UAS7 (Urticaria Activity Score)
   Evaluate efficacy of barzolvolimab on urticaria activity as measured by urticaria activity score (UAS). The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.

Secondary Outcome Measures

1. Mean change from baseline to Week 12 of ISS7 (Itch Severity Score)
   The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The ISS7 is the itch severity score for 7 days, the scores range from 0 to 21.
2. Mean change from baseline to Week 12 of HSS7 (Hives Severity Score)
   The ISS7 and HSS7 combined together make up the UAS7 scoring system to evaluate urticaria signs and symptoms. The HSS7 score is the wheal/hives severity score for 7 days, the scores range from 0 to 21.
3. Percentage of patients with UAS7=0 at Week 12
   Proportion of participants who achieve complete absence of hives and itch (UAS7 = 0) at Week 12.
4. Percentage of participants with UAS7 ≤ 6 at Week 12
   Proportion of participants who achieve control of their urticaria signs and symptoms (UAS7≤6) at Week 12.
5. Percentage of participants with AAS7 > 0 at baseline with AAS7 = 0 at Week 12
   Proportion of participants with AAS7 \> 0 at Day 1 who achieved complete control (AAS7 = 0) at Week 12 Angioedema Activity Score over 7 days \[AAS7\] describes the effect of angioedema on five categories with 0 being none and 3 being most severe. The final score is calculated by adding together daily scores which can range from 0-15 for 7 days. The resulting maximum score is then 105.
6. Mean change from baseline in UAS7 in participants refractory to omalizumab treatment at Week 12
   Evaluate efficacy of barzolvolimab on urticaria activity as measured by urticaria activity score (UAS) in participants who did not respond to or did not tolerate omalizumab. The UAS7 is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42, and a minimum possible score of 0.
7. Proportion of participants with UAS7 = 0 in participants refractory to omalizumab treatment at Week 12
   Proportion of participants who achieve complete absence of hives and itch (UAS7 = 0) at Week 12 in participants who did not respond to or did not tolerate omalizumab.
8. Incidence of Treatment-Emergent Adverse Events
   Occurrence of treatment emergent adverse events and serious adverse events during the study.