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)

Phase 3RecruitingNCT07266402

Celldex Therapeutics240 enrolled

Overview

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. Then there is 16-week follow-up period where all patients are observed.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

240

Conditions

Chronic Inducible Urticaria Cold Urticaria Cold-Induced Urticaria

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 ≥ 10 °C and \< 37 °C using the TempTest® and a numerical rating scale score of ≥ 3 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 ≥ 3 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 of a live vaccine within 2 months prior to study treatment (subjects must agree to avoid vaccination 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.

Outcomes

Primary Outcomes

Complete response to provocation testing at Week 12

Proportion of Cold Induced Urticaria \[ColdU\] participants with complete response in Critical Temperature Threshold (CTT) or proportion of Symptomatic Dermographism \[SD\] participants with complete response in Critical Friction Threshold at Week 12. * For ColdU patients, a complete response is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest® * For SD patients, a complete response test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest®

Time frame: From Day 1 (first dose) to Week 12

Secondary Outcomes

Change from baseline in Critical Temperature Threshold (CTT) at Week 12

For participants with Cold Induced Urticaria, change from baseline in CTT following the TempTest® at Week 12. CTT is defined as threshold temperature at which wheals are triggered (highest temperature for cold), assessed at the 10-minute mark.

Time frame: From Day 1 (first dose) to Week 12

Change from baseline in Critical Friction Threshold (CFT) at Week 12

For participants with Symptomatic Dermographism, change from baseline in CFT following the FricTest® at Week 12. CFT is the threshold pin number at which wheals are triggered, assessed at the 10-minute mark.

Time frame: From Day 1 (first dose) to Week 12

Complete response to provocation testing at Week 24 for Cold Induced Urticaria participants

Proportion of Cold Induced Urticaria participants with complete response in Critical Temperature Threshold (CTT) following the TempTest® 4.0 at Week 24.

Time frame: From Day 1 (first dose) to Week 24

Complete response to provocation testing at Week 24 for Symptomatic Dermographism participants

Proportion of Symptomatic Dermographism participants with complete response in Critical Friction Threshold (CFT) following the FricTest® 4.0 at Week 24

Time frame: From Day 1 (first dose) to Week 24

Change from baseline in Critical Temperature Threshold (CTT) at Week 24

For participants with Cold Induced Urticaria, change from baseline in CTT following the TempTest® at Week 24.

Time frame: From Day 1 (first dose) to Week 24

Change from baseline in Critical Friction Threshold (CFT) at Week 24

For participants with Symptomatic Dermographism, change from baseline in CFT following the FricTest® at Week 24.

Time frame: From Day 1 (first dose) to Week 24

Improvement in clinical symptoms of itch at Week 12

Change from baseline in worst itch-numerical rating scale (WI-NRS) at Week 12 (on a scale of 0-10 in which no itch/burning/pain = 0 and worst ever is = 10).

Time frame: From Day 1 (first dose) to Week 12

Improvement in clinical symptoms of itch at Week 24

Change from baseline in worst itch-numerical rating scale (WI-NRS) at Week 24 (on a scale of 0-10 in which no itch/burning/pain = 0 and worst ever is = 10).

Time frame: From Day 1 (first dose) to Week 24

Change from baseline in WI-NRS following provocation testing (WI-NRSprovo) at Week 12

Change from baseline in WI-NRSprovo at Week 12 (on a scale of 0-10 in which no itch/burning/pain = 0 and worst ever is = 10).

Time frame: From Day 1 (first dose) to Week 12

Complete response to provocation testing at Week 4

Proportion of Cold Induced Urticaria participants with complete response in Critical Temperature Threshold (CTT) following the TempTest® 4.0 at Week 4 or proportion of Symptomatic Dermographism participants with complete response in Critical Friction Threshold (CFT) following the FricTest® 4.0 at Week 4

Time frame: From Day 1 (first dose) to Week 4

Change from baseline in Critical Temperature Threshold (CTT) at Week 4

For participants with Cold Induced Urticaria, change from baseline in CTT following the TempTest® at Week 4.

Time frame: From Day 1 (first dose) to Week 4

Change from baseline in Critical Friction Threshold (CFT) at Week 4

For participants with Symptomatic Dermographism, change from baseline in CFT following the FricTest® at Week 4.

Time frame: From Day 1 (first dose) to Week 4

Improvement in clinical symptoms of hives at Week 12

Change from baseline in worst hives-numerical rating scale (WH-NRS) at Week 12 (on a scale of 0-10 in which no itch/burning/pain = 0 and worst ever is = 10).

Time frame: From Day 1 (first dose) to Week 12

Improvement in clinical symptoms of hives at Week 24

Change from baseline in worst hives-numerical rating scale (WH-NRS) at Week 24 (on a scale of 0-10 in which no itch/burning/pain = 0 and worst ever is = 10).

Time frame: From Day 1 (first dose) to Week 24

Improvement in Dermatology Quality of Life Index (DLQI) at Week 12

Proportion of participants with DLQI = 0-1 at Week 12.

Time frame: From Day 1 (first dose) to Week 12

Incidence of Treatment-Emergent Adverse Events

Occurrence of treatment emergent adverse events, adverse events of special interest and serious adverse events during the study.

Time frame: From Day 1 (first dose) to Week 40

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)

Overview

Conditions

Interventions

Eligibility

Locations (72)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts