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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Celldex Therapeutics
- Enrollment
- 240
- Locations
- 144
- Primary Endpoint
- Complete response to provocation testing at Week 12
Study Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Males and females, >/= 18 years of age.
- •Diagnosis of cold induced urticaria or symptomatic dermographism >/= 3 months.
- •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:
- •The presence of hives for >/= 6 weeks at any time prior to Visit 1 despite the use of H1-antihistamines.
- •Must be on a stable regimen of second generation non-sedating H1-antihistamine for >/= 4 weeks prior to study treatment.
- •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.
- •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.
- •Cold induced urticaria: Positive ice-cube test resulting in hives at the provocation site during Screening
- •Normal blood counts and liver function tests.
- •Both males and females of child-bearing potential must agree to use highly effective contraceptives during the study and for ≥ 150 days after treatment.
- •Willing and able to complete a daily symptom electronic diary and comply with study visits.
- •Participants with and without prior biologic experience are eligible.
Exclusion Criteria
- •Women who are pregnant or nursing.
- •Clearly defined cause for chronic urticaria.
- •Active, pruritic skin condition in addition to cold induced urticaria or symptomatic dermographism.
- •Medical condition that would cause additional risk or interfere with study procedures.
- •Known HIV, hepatitis B or hepatitis C infection.
- •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.
- •History of anaphylaxis, unless due to cold exposure over a large part of the body (such as swimming in cold water).
- •Prior treatment with barzolvolimab
- •There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.
Arms & Interventions
Placebo in patients with Cold Induced Urticaria
Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.
Intervention: Matching Placebo (Drug)
Placebo in patients with Symptomatic Dermographism
Placebo injection subcutaneously every 4 weeks for 24 weeks followed by 300mg barzolvolimab every 8 weeks for 28 weeks.
Intervention: Matching Placebo (Drug)
barzolvolimab in patients with Cold Induced Urticaria
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.
Intervention: Barzolvolimab (Drug)
barzolvolimab in patients with Symptomatic Dermographism
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.
Intervention: Barzolvolimab (Drug)
Outcomes
Primary Outcomes
Complete response to provocation testing at Week 12
Time Frame: From Day 1 (first dose) to 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®
Secondary Outcomes
- Change from baseline in Critical Friction Threshold (CFT) at Week 4(From Day 1 (first dose) to Week 4)
- Improvement in clinical symptoms of hives at Week 12(From Day 1 (first dose) to Week 12)
- Improvement in clinical symptoms of hives at Week 24(From Day 1 (first dose) to Week 24)
- Improvement in Dermatology Quality of Life Index (DLQI) at Week 12(From Day 1 (first dose) to Week 12)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 12(From Day 1 (first dose) to Week 12)
- Change from baseline in Critical Friction Threshold (CFT) at Week 12(From Day 1 (first dose) to Week 12)
- Complete response to provocation testing at Week 24 for Cold Induced Urticaria participants(From Day 1 (first dose) to Week 24)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 24(From Day 1 (first dose) to Week 24)
- Change from baseline in Critical Friction Threshold (CFT) at Week 24(From Day 1 (first dose) to Week 24)
- Improvement in clinical symptoms of itch at Week 12(From Day 1 (first dose) to Week 12)
- Improvement in clinical symptoms of itch at Week 24(From Day 1 (first dose) to Week 24)
- Complete response to provocation testing at Week 4(From Day 1 (first dose) to Week 4)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 4(From Day 1 (first dose) to Week 4)
- Improvement in clinical symptoms of itch at Week 12(From Day 1 (first dose) to Week 12)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 12(From Day 1 (first dose) to Week 12)
- Change from baseline in Critical Friction Threshold (CFT) at Week 12(From Day 1 (first dose) to Week 12)
- Complete response to provocation testing at Week 24 for Cold Induced Urticaria participants(From Day 1 (first dose) to Week 24)
- Complete response to provocation testing at Week 24 for Symptomatic Dermographism participants(From Day 1 (first dose) to Week 24)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 24(From Day 1 (first dose) to Week 24)
- Change from baseline in Critical Friction Threshold (CFT) at Week 24(From Day 1 (first dose) to Week 24)
- Improvement in clinical symptoms of itch at Week 24(From Day 1 (first dose) to Week 24)
- Change from baseline in WI-NRS following provocation testing (WI-NRSprovo) at Week 12(From Day 1 (first dose) to Week 12)
- Complete response to provocation testing at Week 4(From Day 1 (first dose) to Week 4)
- Change from baseline in Critical Temperature Threshold (CTT) at Week 4(From Day 1 (first dose) to Week 4)
- Change from baseline in Critical Friction Threshold (CFT) at Week 4(From Day 1 (first dose) to Week 4)
- Improvement in clinical symptoms of hives at Week 12(From Day 1 (first dose) to Week 12)
- Improvement in clinical symptoms of hives at Week 24(From Day 1 (first dose) to Week 24)
- Improvement in Dermatology Quality of Life Index (DLQI) at Week 12(From Day 1 (first dose) to Week 12)
- Incidence of Treatment-Emergent Adverse Events(From Day 1 (first dose) to Week 40)