A Study of CDX-0159 in Patients With Chronic Inducible Urticaria

Study Overview
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Brief Summary
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The purpose of this study is to assess the clinical effect, the pharmacodynamics, the safety, and the pharmacokinetics of barzolvolimab (CDX-0159) in patients with Chronic Inducible Urticaria who remain symptomatic despite the use of H1-antihistamines.

Detailed Description
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The purpose of this study is to assess the clinical effect, the pharmacodynamics, the safety, and the pharmacokinetics of barzolvolimab in patients with Chronic Inducible Urticaria (Cold 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 20-week treatment period where patients will receive either barzolvolimab 150mg, 300mg or placebo, and then a 24-week follow up period where all patients are observed.

Official Title
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: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Dose-ranging Study to Assess the Efficacy and Safety of CDX-0159 in Patients With Chronic Inducible Urticaria

Conditions
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Chronic Inducible Urticaria

Intervention / Treatment
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* Biological: barzolvolimab
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Males and females, >/= 18 years of age. Diagnosis of chronic ColdU or SD >/= 3 months. Diagnosis of ColdU or SD despite the use of a stable regimen of second generation non-sedating H1-antihistamine as defined by: Recurrent pruritic wheals with or without angioedema due to ColdU or SD 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 and agree to stay on through trial. UCT < 12 during the 14 days prior to treatment. Positive provocation test for ColdU patients: developing a wheal at the test site within 10 min after using TempTest® at any temperature at both screening (Visit 1) and randomization (Visit 3) for SD patients: developing a wheal at the test site within 10 min after using FricTest® with ≥ 3 pins at both screening (Visit 1) and randomization (Visit 3) 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. Key exclusion criteria: Women who are pregnant or nursing. Active Chronic spontaneous urticaria or other forms of CIndU besides ColdU or SD that may interfere with study assessments. Active, pruritic skin condition in addition to CIndU. Medical condition that would cause additional risk or interfere with study procedures. Known active HIV, hepatitis B or hepatitis C infection. 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. History of anaphylaxis There are additional criteria that your study doctor will review with you to confirm you are eligible for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: barzolvolimab 150 mg in patients with Symptomatic Dermographism<br>barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: barzolvolimab 300 mg in patients with Symptomatic Dermographism<br>barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Placebo Comparator: Placebo Comparator in patients with Symptomatic Dermographism<br>Placebo injection subcutaneous every 4 weeks for 20 weeks | Drug: Matching Placebo<br>* Subcutaneous Administration<br>|
| Experimental: barzolvolimab 150 mg in patients with Chronic Inducible Cold Urticaria<br>barzolvolimab 150 mg injection subcutaneous every 4 weeks for 20 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: barzolvolimab 300 mg in patients with Chronic Inducible Cold Urticaria<br>barzolvolimab 300 mg injection subcutaneous every 8 weeks for 20 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Placebo Comparator: Placebo Comparator in patients with Chronic Inducible Cold Urticaria<br>Placebo injection subcutaneous every 4 weeks for 20 weeks | Drug: Matching Placebo<br>* Subcutaneous Administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a negative provocation test at week 12 | Percentage of patients with a negative provocation test for Cold Inducible Urticaria [ColdU] or Symptomatic Dermographism [SD]) at week 12 For ColdU patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at ≤ 4°C after provocation using TempTest® For SD patients, a negative provocation test is defined as absence of wheals at the provocation site within 10 min at 0 pins after provocation using the FricTest® | From baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in provocation threshold and itch for ColdU | Mean change from baseline to week 12 in critical temperature threshold (CTT) in patients with ColdU CTT is defined as threshold temperature at which wheals are triggered (highest temperature for cold), assessed at the 10-minute mark | From baseline to week 12 | 
| Change in provocation threshold for SD | Mean change from baseline to Week 12 in Critical Friction Threshold (CFT) in patients with SD CFT is the threshold pin number at which wheals are triggered, assessed at the 10-minute mark | From baseline to week 12 | 
| Change in worst itch reported after provocation for ColdU | Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with ColdU | From baseline to week 12 | 
| Combined patients with a negative provocation test at week 12 | Percentage of combined patients with a negative TempTest (ColdU) or FricTest (SD) at week 12 | From baseline to week 12 | 
| Change in worst itch reported after provocation for SD | Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with SD | From baseline to week 12 | 
| Change in worst itch reported after provocation in both SD and ColdU | Mean change in worst itch reported by numerical rating scale after provocation testing from baseline to week 12 in patients with SD and ColdU combined | From baseline to week 12 | 
| Percentage of patients experiencing adverse events | Percentage of patients experiencing treatment-emergent adverse events (TEAE) examined by ColdU patients, SD patients and in combination. A TEAE is any untoward medical occurrence in a patient administered a study treatment. | From baseline to week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDX-0159, barzolvolimab