A Phase 2 Study of CDX-0159 in Patients With Chronic Spontaneous 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 Spontaneous Urticaria

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 Spontaneous Urticaria. There is a screening period of up to 4 weeks, followed by a 16-week placebo-controlled treatment period (Placebo-Controlled Treatment Phase) where patients will receive either barzolvolimab at a dose level of 75mg, 150mg, or 300mg, or placebo, and then a 36-week treatment period where all patients will receive barzolvolimab. Patients who receive barzolvolimab 75mg or placebo in the placebo-controlled treatment phase will be re-randomized to receive either barzolvolimab 150mg or 300mg in the active treatment phase.

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

Conditions
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Chronic Spontaneous 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 spontaneous urticaria (CSU) >/= 6 months. Diagnosis of CSU 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. UAS7 of >/= 16 and ISS7 of >/= 8 during the 7 days prior to treatment. 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. Key exclusion criteria: Women who are pregnant or nursing. Clearly defined cause for chronic urticaria. Active, pruritic skin condition in addition to CSU. 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 Prior treatment with barzolvolimab 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 75 mg then 150 mg<br>barzolvolimab 75 mg injection subcutaneous every 4 weeks for 16 weeks and then 150 mg injection subcutaneous every 4 weeks for 36 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: barzolvolimab 75 mg then 300 mg<br>barzolvolimab 75 mg injection subcutaneous every 4 weeks for 16 weeks and then 300 mg injection subcutaneous every 8 weeks for 36 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: barzolvolimab 150 mg<br>barzolvolimab 150 mg injection subcutaneous every 4 weeks for 52 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: barzolvolimab 300 mg<br>barzolvolimab 300 mg injection subcutaneous every 8 weeks for 52 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;|
| Experimental: Placebo then barzolvolimab 150 mg<br>Placebo injection subcutaneous every 4 weeks for 16 weeks and then barzolvolimab 150 mg injection subcutaneous every 4 weeks for 36 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;Drug: Matching Placebo<br>* Subcutaneous Administration<br>|
| Experimental: Placebo then barzolvolimab 300 mg<br>Placebo injection subcutaneous every 4 weeks for 16 weeks and then barzolvolimab 300 mg injection subcutaneous every 8 weeks for 36 weeks | Biological: barzolvolimab<br>* Subcutaneous Administration<br>* Other names: CDX-0159;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 |
| --- | --- | --- |
| Mean change from baseline to Week 12 of UAS7 (Urticaria Activity Score) | Evaluate efficacy of barzolvolimab on urticaria activity as measured by urticaria activity score (UAS). UAS7 is the sum of the itch severity score measured over 7 days (ISS7) and the hives severity score measured over 7 days (HSS7). The possible range of UAS7 is 0 - 42. Itch severity score (ISS) is on a scale of 0 - 3. 0 = None = mild (present, but not annoying or troublesome) = moderate (troublesome, but does not interfere with normal daily activity or sleep) = intense (severe itch, which is sufficiently troublesome to interfere with normal daily activity or sleep) Hives severity score (HSS) is on a scale of 0 - 3. 0 = None = less than 20 hives = between 20 and 50 hives = greater than 50 hives | From baseline to Day 85 (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline to Week 12 of ISS7 (Itch Severity Score) | ISS7 is derived by adding up the daily scores over 7 days. The possible range of the weekly score is 0 -21. | From baseline to Day 85 (Week 12) | 
| Mean change from baseline to Week 12 of HSS7 (Hives Severity Score) | HSS7 is derived by adding up the daily scores over 7 days. The possible range of the weekly score is 0 -21. | From baseline to Day 85 (Week 12) | 
| Mean change from baseline to Week 12 of AAS7 (Angioedema Activity Score) | AAS captures the presences of swelling over the last 24 hours and rates the severity with 5 questions. The possible range of the weekly score is 0 - 105. | From baseline to Day 85 (Week 12) | 

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