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

Phase 2

Completed

Conditions: Chronic Spontaneous Urticaria

Interventions: Other: Placebo
Biological: QGE031
Biological: Omalizumab

Registration Number: NCT02477332

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 382

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo s.c. q4w	Placebo	placebo injection subcutaneous every 4 weeks
QGE031 240 mg s.c. q4w	QGE031	ligelizumab 240 mg injection subcutaneous every 4 weeks
QGE031 120 mg s.c. s.d.	QGE031	ligelizumab 120 mg injection subcutaneous single dose
QGE031 24 mg s.c. q4w	QGE031	ligelizumab 24 mg injection subcutaneous every 4 weeks
QGE031 72 mg s.c. q4w	QGE031	ligelizumab 72 mg injection subcutaneous every 4 weeks
Omalizumab 300 mg s.c. q4w	Omalizumab	omalizumab 300 mg injection subcutaneous every 4 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Complete Hives Response (HSS7=0)	Week 12	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 1. - Mild (1-6 hives/12 hours) 2. - Moderate (7-12 hives/12 hours) 3. - 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.

Secondary Outcome Measures

Name	Time	Method
HSS7=0 Response: at Week 20 Measured Over 7 Days	Week 20	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 1. - Mild (1-6 hives/12 hours) 2. - Moderate (7-12 hives/12 hours) 3. - Severe (\>12 hives/12 hours)
UAS7=0 Response: at Week 20 Measured Over 7 Days	Week 20	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.
Complete Hives Response (HSS7=0) Rate at Week 12 Measured Over 7 Days	Week 12	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 1. - Mild (1-6 hives/12 hours) 2. - Moderate (7-12 hives/12 hours) 3. - Severe (\>12 hives/12 hours)
Change From Baseline in Hives Severity Score (HSS7) at Week 20 Measured Over 7 Days	Week 20	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 1. - Mild (1-6 hives/12 hours) 2. - Moderate (7-12 hives/12 hours) 3. - Severe (\>12 hives/12 hours)
Change From Baseline in Itch Severity Score (ISS7) at Week 20 Measured Over 7 Days	Week 20	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 1. - Mild (minimal awareness, easily tolerated) 2. - Moderate (definite awareness, bothersome but tolerable) 3. - Severe (difficult to tolerate)
Change From Baseline in Urticaria Activity Score (UAS7) at Week 20 Measured Over 7 Days	Week 20	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42.
ISS7=0 Response: at Week 20 Measured Over 7 Days	Week 20	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 1. - Mild (minimal awareness, easily tolerated) 2. - Moderate (definite awareness, bothersome but tolerable) 3. - Severe (difficult to tolerate)
Change From Baseline in Itch Severity Score (ISS7) at Week 12 Measured Over 7 Days	Week 12	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 1. - Mild (minimal awareness, easily tolerated) 2. - Moderate (definite awareness, bothersome but tolerable) 3. - Severe (difficult to tolerate)
Change From Baseline in Urticaria Activity Score (UAS7) at Week 12 Measured Over 7 Days	Week 12	UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42.
Change From Baseline in Hives Severity Score (HSS7) at Week 12 Measured Over 7 Days	Week 12	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 1. - Mild (1-6 hives/12 hours) 2. - Moderate (7-12 hives/12 hours) 3. - Severe (\>12 hives/12 hours)
Complete Urticaria Activity Score Response (UAS7=0) Rate at Week 12 Measured Over 7 Days	Week 12	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.
Complete Itch Response (ISS7=0) Rate at Week 12 Measured Over 7 Days	Week 12	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 1. - Mild (minimal awareness, easily tolerated) 2. - Moderate (definite awareness, bothersome but tolerable) 3. - Severe (difficult to tolerate)