A Safety and Efficacy Study of Ligelizumab in the Treatment of CSU in Japanese Patients Inadequately Controlled With H1- Antihistamines

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ligelizumab in adult Japanese subjects with CSU, who remain symptomatic despite treatment with H1-antihistamines (AHs) at locally approved doses. The study population will consist of approximately 65 male and female subjects aged ≥ 18 years who have been diagnosed with CSU and who remain symptomatic despite the use of H1-AH. This is a Phase III multi-center, open-label, single arm study. There is a screening period of up to 28 days, a 52 week treatment period, and a 12 week post-treatment follow-up period.

Official Title
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A Multi-center, Open-label Study to Investigate the Safety/Tolerability and Efficacy of Ligelizumab (QGE031) in the Treatment of Adult Japanese Patients With Chronic Spontaneous Urticaria (CSU) Inadequately Controlled With H1 Antihistamines

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Biological: Ligelizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Male and female subjects ≥ 18 years of age at the time of screening CSU diagnosis for ≥ 6 months Diagnosis of CSU refractory to H1-AH at approved doses at the time of Baseline (Visit 110, Day 1), as defined by all of the following: The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1 (Day -28 to Day -14) despite current use of non-sedating H1-AH (at locally approved doses) during this time period UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to baseline (Visit 110, Day 1) Subjects must be on H1-AH at only approved doses for treatment of CSU for starting at Visit 1 (Day -28 to Day -14) Willing and able to complete a daily symptom electronic Diary (eDiary) for the duration of the study and adhere to the study visit schedules Key Exclusion Criteria: History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes (i.e. to murine, chimeric, or human antibodies) Subjects having a clearly defined, predominant trigger of their chronic urticaria (CU) (chronic inducible urticaria (CINDU)) including - urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency) Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All subjects will be screened at Visit 1. If stool testing is positive for pathogenic organism, the subject will not enter treatment period and will not be allowed to rescreen Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid (BP), dermatitis herpetiformis, senile pruritus, etc) Prior exposure to ligelizumab Any H2 antihistamine, Leukotriene Receptor Antagonist (LTRA) (montelukast or zafirlukast) or H1 antihistamines use at greater than approved dose after Visit 1 Other protocol-defined inclusion/exclusion criteria may apply.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ligelizumab<br>Ligelizumab q4w | Biological: Ligelizumab<br>* Liquid in vial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability for 12 months | Overall safety data assessed as treatment emergent adverse events during the study | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UAS7 change from baseline over time | Assessed as absolute change from baseline of UAS7 by visit up to end of study. The Urticaria Activity Score (UAS) is the sum of Hive Severity Score (HSS) and Itch Severiry Score (ISS). The HSS has a scale of 0 (none) to 3 (intense/severe). A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days. The ISS also has a scale of 0 (none) to 3 (severe/difficult to tolerate). A weekly score (ISS7) is derived by adding up the average daily scores of the preceding 7 days. The UAS7 is the sum of the HSS7 score and the ISS7 score, and has a possible range in score of 0-42. | Baseline, every 4 weeks to Week 64 | 
| HSS7 change from baseline over time | Assessed as absolute change from baseline of HSS7 by visit up to end of study. | Baseline, every 4 weeks to Week 64 | 
| ISS7 change from baseline over time | Assessed as absolute change from baseline of ISS7 by visit up to end of study. | Baseline, every 4 weeks to Week 64 | 
| Achievement of the complete UAS7 = 0 response over time | Assessed as proportion of subjects with UAS7 = 0 response by visit up to the end of study. | Baseline, every 4 weeks to Week 64 | 
| Achievement of the complete HSS7 = 0 response over time | Assessed as proportion of subjects with HSS7 = 0 response by visit up to the end of study. | Baseline, every 4 weeks to Week 64 | 
| Achievement of the complete ISS7 = 0 response over time | Assessed as proportion of subjects with ISS7 = 0 response by visit up to the end of study. | Baseline, every 4 weeks to Week 64 | 
| Profile of change from baseline in the Dermatology Life Quality Index (DLQI) | Assessed by absolute change from baseline of DLQI by visit up to end of study | Baseline, Week 4, 8, 12, 24, 52, 56, 60 and 64. | 
| Achievement of DLQI = 0/1 by visit up to end of study | Assessed as proportion of subjects with DLQI = 0/1 by visit up to end of study | Baseline, Week 4, 8, 12, 24, 52, 56, 60 and 64 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CSU (chronic spontaneous urticaria), Japanese, QGE031, Anti-IgE, Ligelizumab