A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria

Study Overview
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Brief Summary
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The reason for this study is to see if the study drug LY3454738 is safe and effective as treatment for participants with hives that are caused by chronic spontaneous urticaria (CSU) and that are not controlled with H1-antihistamines.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Crossover Study to Evaluate the Efficacy and Safety of LY3454738 in Adults With Chronic Spontaneous Urticaria Inadequately Controlled With H1-Antihistamines

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Drug: LY3454738
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must agree to use appropriate birth control throughout the study Must have a diagnosis of CSU for at least 6 months Must have CSU symptoms for at least 8 consecutive weeks despite taking anti-histamines Must agree to take an anti-histamine every day during the trial Must be willing to enter information about symptoms in an electronic diary twice a day Exclusion Criteria: Must not have a cause, other than CSU, for itching, hives, and/or angioedema (swelling beneath the skin) Must not have a current or recent active infection requiring antibiotics Must not have a history of anaphylaxis (severe, life threatening allergic reaction) Must not have asthma requiring medications other than short acting beta agonists (albuterol, etc.) Must not have received prior treatment with omalizumab, ligelizumab, or other experimental biologic for CSU

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3454738<br>500 milligram (mg) LY3454738 administered intravenously (IV). | Drug: LY3454738<br>* Administered IV<br>|
| Placebo Comparator: Placebo<br>Placebo administered IV. | Drug: Placebo<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity.The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) | The ISS7 is the sum of the daily ISS over a 7-day period and ranges from 0 to 21. The daily ISS is the average of the morning and evening ISS on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The baseline ISS7 is the sum of the daily ISS over the 7 days prior to the first treatment. A higher ISS or higher ISS7 indicates more severe itching. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). | Baseline, Week 12 | 
| Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) | The HSS7 is the sum of the daily number of hives over a 7-day period and ranges from 0 to 21. The daily number of hives score (also called HSS) is the average of the morning and evening number of hive scores on a four-point scale of 0 (none), 1 (between 1 and 6 hives, inclusive), 2 (between 7 and 12 hives, inclusive), and 3 (greater than 12 hives). The baseline weekly HSS7 is the sum of the HSS over the 7 days prior to the first treatment. A higher HSS or higher HSS7 indicates a greater number of hives. The ANCOVA model includes treatment as a factor and baseline UAS7 score in First 12-Week treatment period as covariates. Missing Week 12 scores will be imputed by carrying forward the participants' baseline scores (BOCF). | Baseline, Week 12 | 
| Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< 28 vs >= 28) Score) | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42. The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity. | Week 12 | 
| Percentage of Participants Achieving Urticaria Activity Score Over 7 Days (UAS7) ≤6 (Stratified by Baseline UAS7 (< Median vs >= Median) Score) | The UAS7 is the sum of the daily urticaria activity scores (UAS) over a 7-day period and ranges from 0 to 42.The daily UAS is the sum of the daily itch severity score (ISS) and daily number of hives score, and ranges from 0 to 6. The baseline UAS7 is the sum of the daily UAS over the 7 days prior to the first treatment. A higher UAS or higher UAS7 indicates greater urticaria disease activity. | Week 12 | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 336 Hours (AUC [0-336h]) of LY3454738 | Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up | 
| PK: Maximum Concentration (Cmax) of LY3454738 | PK: Maximum Concentration (Cmax) of LY3454738 | Before Infusion, after infusion, 1 hour after infusion and 2 hours after infusion on Day 1; Before Infusion on Day 8, 15, 29, 43, 57, 71, 85, 92, 99, 113, 127, 141, 155, 169 and Post-Treatment Follow-up |