Study of Efficacy and Safety of Ligelizumab in Adolescents and Adults With Chronic Inducible Urticaria Who Remain Symptomatic Despite Treatment With H1- Antihistamines

Study Overview
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Brief Summary
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This was a placebo controlled, phase 3 study designed to evaluate the efficacy and safety of ligelizumab in participants with chronic inducible urticaria who are inadequately controlled with H1-antihistamines

Detailed Description
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There are currently no approved therapies for patients with CINDU who remain symptomatic despite treatment with H1-antihistamines. The purpose of this study was to establish efficacy and safety of ligelizumab (QGE031) over placebo in participants with chronic inducible urticaria (CINDU) who remain symptomatic despite treatment with H1 antihistamine.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety of Ligelizumab (QGE031) in the Treatment of Chronic Inducible Urticaria (CINDU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines

Conditions
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Chronic Inducible Urticaria

Intervention / Treatment
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* Drug: Ligelizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months. Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic urticaria) inadequately controlled with H1-AH at local label approved doses at the time of randomization, as defined by all of the following: Positive response (i.e development of symptoms) to triggers despite treatment with H1-AH Positive response (i.e. development of symptoms) to provocation test on day of randomization Participants must be able to physically perform the protocol defined provocation test specific to the participant's CINDU. Cholinergic urticaria participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included. Willing and able to complete a daily symptom eDiary as per protocol requirement and adhere to the study visit schedules Exclusion Criteria: History of hypersensitivity to any of the study drugs or its components or to drugs of similar chemical classes or to the provocation test or items used in provocation tests Participants who have concomitant CSU at screening Participants who have a familial form of the target CINDU that is being considered for the participant's inclusion in this study Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study Diseases, other than chronic inducible urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency). Any other skin disease associated with chronic itching that might influence, in the investigator's opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism Prior exposure to ligelizumab, omalizumab and or other anti-IgE therapies

Ages Eligible for Study
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Minimum Age: 12 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ligelizumab low dose, symptomatic dermographism group<br>Ligelizumab low dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism | Drug: Ligelizumab<br>* Ligelizumab treated groups and arms<br>* Other names: QGE031;|
| Experimental: Ligelizumab high dose, symptomatic dermographism<br>Ligelizumab high dose subcutaneous injection every 4 weeks in participants with symptomatic dermographism | Drug: Ligelizumab<br>* Ligelizumab treated groups and arms<br>* Other names: QGE031;|
| Placebo Comparator: Placebo SC q4W, symptomatic dermographism<br>Placebo subcutaneous injection every 4 weeks in participants with symptomatic dermographism | Other: Placebo<br>* Placebo treated groups and arms<br>|
| Experimental: Ligelizumab low dose, cold urticaria<br>Ligelizumab low dose subcutaneous injection every 4 weeks in participants with cold urticaria | Drug: Ligelizumab<br>* Ligelizumab treated groups and arms<br>* Other names: QGE031;|
| Experimental: Ligelizumab high dose, cold urticaria<br>Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cold urticaria | Drug: Ligelizumab<br>* Ligelizumab treated groups and arms<br>* Other names: QGE031;|
| Placebo Comparator: Placebo SC q4w, cold urticaria<br>Placebo subcutaneous injection every 4 weeks in participants with cold urticaria | Other: Placebo<br>* Placebo treated groups and arms<br>|
| Experimental: Ligelizumab high dose, cholinergic urticaria<br>Ligelizumab high dose subcutaneous injections every 4 weeks in participants with cholinergic urticaria | Drug: Ligelizumab<br>* Ligelizumab treated groups and arms<br>* Other names: QGE031;|
| Placebo Comparator: Placebo SC q4w, cholinergic urticaria<br>Placebo subcutaneous injections every 4 weeks in participants with cholinergic urticaria | Other: Placebo<br>* Placebo treated groups and arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Fric Score in Participants With Symptomatic Dermographism | Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width) None of the participants completed Week 12 and hence at Week 12 was not analyzed | Baseline, Week 12 | 
| Change From Baseline in Critical Temperature Threshold in Participants With Cold Urticaria | The TempTest is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms. | Baseline, Week 12 | 
| Change From Baseline in Itch Numerical Rating Scale in Participants With Cholinergic Urticaria | Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement. Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 (no itch) to 10 (worst possible itch) | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Symptomatic Dermographism With Total Fric Score = 0 | Total Fric score (a scale of 0-4 where 0= no linear hive ≥ 3mm in width, 1= one linear hive ≥ 3mm in width, 2= two linear hives ≥ 3mm in width, 3= three linear hives ≥ 3mm in width and 4 = four linear hives ≥ 3mm in width) None of the participants completed Week 12 | Week 12 | 
| Change From Baseline in Itch Numerical Rating Scale in Participants With Symptomatic Dermographism | Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement. Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 (no itch) to 10 (worst possible itch) | Baseline, Week 12 | 
| Proportion of Participants With Cold Urticaria With Complete Response (no Itch or Hives) to the TempTest | The TempTest® is used to induce itch and hives in participants with cold urticaria. Critical temperature threshold (CTT), as measured by the TempTest, determines the highest temperature sufficient for inducing symptoms. | Baseline, Week 12 | 
| Change From Baseline in Itch Numerical Rating Scale in Participants With Cold Urticaria | Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement. Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 (no itch) to 10 (worst possible itch) | Baseline, Week 12 | 
| Proportion of Participants With Cholinergic Urticaria With Itch Numerical Rating Scale =0 | Itch numerical rating scale, a scale from 0 to 10. Negative change from baseline indicates improvement. Patients were asked to rate itching severity based on the worst level of itching in the past 24 h using an 11-point scale from 0 (no itch) to 10 (worst possible itch) | Week 12 | 
| Proportion of Participants With Cholinergic Urticaria With Physician Global Assessment of Severity of Hives (PGA - Hive Score) =0 | Physician global assessment of severity of hives PGA is an assessment of all lesions scored on a scale from 0-5 (with 0 = No hives and 5 = Very severe hives) | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ligelizumab, anti-IgE, CINDU, chronic inducible urticaria, symptomatic dermographism, cold urticaria, cholinergic urticaria, urticaria, itch, hives