Dose-finding Study of QGE031 as add-on Therapy to Evaluate Efficacy and Safety in Patients With CSU

Study Overview
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Brief Summary
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This is a placebo and active-controlled phase 2b dose-finding study to evaluate efficacy and safety of QGE031 monthly subcutaneous injections as add-on therapy in patients with Chronic Spontaneous Urticaria.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo, and Active-controlled Phase 2b Dose-finding Study of QGE031 as add-on Therapy to Investigate the Efficacy and Safety in Patients With Chronic Spontaneous Urticaria (CSU)

Conditions
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Chronic Spontaneous Urticaria

Intervention / Treatment
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* Biological: QGE031
* Biological: Omalizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic spontaneous urticaria for at least 6 months Diagnosis of chronic spontaneous urticaria refractory to standard of care at time of randomization Exclusion Criteria: Clearly defined underlying etiology for chronic urticaria other than chronic spontaneous urticaria Evidence of parasitic infection Any other skin disease with chronic itching Previous treatment with omalizumab or QGE031 Contraindications to or hypersensitivity to fexofenadine, loratadine, cetirizine, or epinephrine History of anaphylaxis History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study History of hypersensitivity to any of the study drugs or its components of similar chemical classes Pregnant or nursing (lactating) women Other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: QGE031 24 mg s.c. q4w<br>ligelizumab 24 mg injection subcutaneous every 4 weeks | Biological: QGE031<br> <br> |
| Experimental: QGE031 72 mg s.c. q4w<br>ligelizumab 72 mg injection subcutaneous every 4 weeks | Biological: QGE031<br> <br> |
| Experimental: QGE031 240 mg s.c. q4w<br>ligelizumab 240 mg injection subcutaneous every 4 weeks | Biological: QGE031<br> <br> |
| Active Comparator: Omalizumab 300 mg s.c. q4w<br>omalizumab 300 mg injection subcutaneous every 4 weeks | Biological: Omalizumab<br> <br> |
| Placebo Comparator: Placebo s.c. q4w<br>placebo injection subcutaneous every 4 weeks | Other: Placebo<br> <br> |
| Experimental: QGE031 120 mg s.c. s.d.<br>ligelizumab 120 mg injection subcutaneous single dose | Biological: QGE031<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Complete Hives Response (HSS7=0) | The primary objective was to establish the dose-response relationship of ligelizumab (24, 72 and 240 mg every 4 weeks) with respect to achievement of complete hives response (HSS7=0) at Week 12 and select an appropriate dose (or range of doses) which is likely to be superior to omalizumab at the highest approved dose (300 mg every 4 weeks). Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the preceding 7 days, with a possible range of 0 - 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) To confirm an overall dose-response signal based on MCP-Mod, and to estimate the minimal ligelizumab dose that shows a relevant superior effect over omalizumab, based on the selected dose response model, the lowest ligelizumab dose that provides a response rate 15% higher than the response of omalizumab 300 mg. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Hives Response (HSS7=0) Rate at Week 12 Measured Over 7 Days | Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 0. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) | Week 12 | 
| Change From Baseline in Hives Severity Score (HSS7) at Week 12 Measured Over 7 Days | Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) | Week 12 | 
| HSS7=0 Response: at Week 20 Measured Over 7 Days | Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete hives response defined as HSS7 = 0. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) | Week 20 | 
| Change From Baseline in Hives Severity Score (HSS7) at Week 20 Measured Over 7 Days | Hives Severity Score (HSS) is on a scale of 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None - Mild (1-6 hives/12 hours) - Moderate (7-12 hives/12 hours) - Severe (>12 hives/12 hours) | Week 20 | 
| Change From Baseline in Itch Severity Score (ISS7) at Week 12 Measured Over 7 Days | Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate) | Week 12 | 
| Change From Baseline in Itch Severity Score (ISS7) at Week 20 Measured Over 7 Days | Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate) | Week 20 | 
| Change From Baseline in Urticaria Activity Score (UAS7) at Week 12 Measured Over 7 Days | UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. | Week 12 | 
| Change From Baseline in Urticaria Activity Score (UAS7) at Week 20 Measured Over 7 Days | UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. | Week 20 | 
| Complete Urticaria Activity Score Response (UAS7=0) Rate at Week 12 Measured Over 7 Days | UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete urticaria activity response is defined as UAS7 = 0. | Week 12 | 
| UAS7=0 Response: at Week 20 Measured Over 7 Days | UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete urticaria activity response is defined as UAS7 = 0. | Week 20 | 
| Complete Itch Response (ISS7=0) Rate at Week 12 Measured Over 7 Days | Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate) | Week 12 | 
| ISS7=0 Response: at Week 20 Measured Over 7 Days | Itch Severity Score (ISS) is on a scale of 0 to 3. A weekly score (ISS7) is derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score is therefore 0 to 21. Complete itch response defined as ISS7 = 0. Itch Severity Score scale: 0 - None - Mild (minimal awareness, easily tolerated) - Moderate (definite awareness, bothersome but tolerable) - Severe (difficult to tolerate) | Week 20 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QGE031, ligelizumab, omalizumab, chronic, spontaneous, urticaria, adults, CSU