A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD)

A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study of Barzolvolimab in Participants With Cold Induced Urticaria and Symptomatic Dermographism (EMBARQ-COLDU and SD)

The purpose of this Phase 3, randomized, double-blind, placebo-controlled study is to assess the activity and safety of barzolvolimab compared to placebo in participants with cold induced urticaria or symptomatic dermographism who remain symptomatic despite the use of H1-antihistamines.

The purpose of this Phase 3, randomized, double-blind, placebo-controlled study is to assess the activity and safety of barzolvolimab compared to placebo in participants with cold induced urticaria (ColdU) or symptomatic dermographism (SD) who remain symptomatic despite the use of H1-antihistamines.

There is a Screening Period of up to 4 weeks, followed by a 24-week treatment period where patients will receive barzolvolimab or placebo. Patients receiving barzolvolimab will receive 450mg at the start of the treatment period and then 150mg every 4 weeks. Then there is a 28-week treatment period where all patients will receive 300mg barzolvolimab every 8 weeks, followed by a 16-week follow-up period where all patients are observed.

Key Inclusion Criteria:

1. Males and females, >/= 18 years of age.

2. Diagnosis of cold induced urticaria or symptomatic dermographism >/= 3 months.

3. Diagnosis of cold induced urticaria or symptomatic dermographism despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by:

   1. The presence of hives for >/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
   2. Must be on a stable regimen of second generation non-sedating H1-antihistamine for >/= 4 weeks prior to study treatment.
   3. Cold induced urticaria: A Critical Threshold Temperature (CTT) of ≥ 15 °C and < 37 °C using the TempTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.
   4. Symptomatic dermographism: A Critical Friction Threshold (CFT) of ≥ 3 using the FricTest® and a numerical rating scale score of ≥ 5 for itch after the provocation test.

4. Cold induced urticaria: Positive ice-cube test resulting in hives at the provocation site during Screening

5. Normal blood counts and liver function tests.

6. Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for ≥ 150 days after treatment.

7. Willing and able to complete a daily symptom electronic diary and comply with study visits.

8. Participants with and without prior biologic experience are eligible.

Key Exclusion Criteria:

1. Women who are pregnant or nursing.
2. Clearly defined cause for chronic urticaria.
3. Active, pruritic skin condition in addition to cold induced urticaria or symptomatic dermographism.
4. Medical condition that would cause additional risk or interfere with study procedures.
5. Known HIV, hepatitis B or hepatitis C infection.
6. Vaccination with a live vaccine within 30 days prior to screening (subjects must agree to avoid vaccination with a live vaccine during the study). Inactivated vaccines are allowed such as seasonal influenza injection or COVID-19 vaccine.
7. History of anaphylaxis, unless due to cold exposure over a large part of the body (such as swimming in cold water).
8. Prior treatment with barzolvolimab

There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.