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)

Celldex Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Cold-Induced Urticaria; Chronic Inducible Urticaria; Symptomatic Dermographism; Cold Urticaria

Treatments: Drug: Matching Placebo; Drug: Barzolvolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT07266402

CDX0159-16

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

240 participants in 4 patient groups, including a placebo group

barzolvolimab in patients with Cold Induced Urticaria

Experimental group

Description:

barzolvolimab 450mg injection subcutaneously at randomization , then 150mg injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.

Treatment:

Drug: Barzolvolimab

Placebo in patients with Cold Induced Urticaria

Placebo Comparator group

Description:

Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.

Treatment:

Drug: Matching Placebo

barzolvolimab in patients with Symptomatic Dermographism

Experimental group

Description:

barzolvolimab 450mg injection subcutaneously at randomization, then 150mg injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.

Treatment:

Drug: Barzolvolimab

Placebo in patients with Symptomatic Dermographism

Placebo Comparator group

Description:

Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.

Treatment:

Drug: Matching Placebo