Study of Efficacy and Safety of Ligelizumab in Chronic Spontaneous Urticaria Patients Who Completed a Previous Study With Ligelizumab

Chronic Spontaneous Urticaria Clinical Trial

Official title:

A Multi-center, Double-blinded and Open-label Extension Study to Evaluate the Efficacy and Safety of Ligelizumab as Retreatment, Self-administered Therapy and Monotherapy in Chronic Spontaneous Urticaria Patients Who Completed Studies CQGE031C2302, CQGE031C2303, CQGE031C2202 or CQGE031C1301

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04210843
• Other study ID #: CQGE031C2302E1
• Secondary ID: 2019-001792-37
• Status: Terminated
• Phase: Phase 3
• Start date: April 8, 2020
• Est. completion date: September 1, 2022

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this extension study was to establish efficacy and safety of ligelizumab. This was assessed in adult and adolescent chronic spontaneous urticaria (CSU) patients who had completed a preceding ligelizumab study and have relapsed, following treatment in these preceding studies, despite standard of care H1-antihistamine (H1-AH) treatment.

This study also fulfilled the Novartis commitment to provide post-trial access to patients who had completed studies: CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878).

Description:

This was a Phase IIIb multi-center, double-blinded and open-label extension study to evaluate efficacy and safety of ligelizumab retreatment with H1-AHs background therapy with an option for ligelizumab monotherapy (i.e., discontinuation of background H1-AH) in adult and adolescent CSU participants who had completed one of the preceding studies, in the setting of retreatment and self-administration.

Participants with weekly urticaria activity score (UAS7) < 16 during screening entered the first (investigational treatment-free) observation period (OBS1), with a duration up to 36 weeks.

Participants with UAS7 ≥ 16 during screening or OBS1 were assigned to 1 of the 2 treatment arms and entered the treatment period (first half treatment period, referred to as TRT1). The first half treatment period (TRT1) was 52 weeks (from Week 0 to Week 52). Participants remained on the same H1-AH background medication they were taking in the preceding studies. TRT1 was divided into:

• The first 12 weeks in TRT1:

i. participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) previously treated with ligelizumab 72 mg liquid in vial subcutaneously (s.c.) every 4 weeks (Q4W) were treated with the same dose regimen in a double-blind manner in this extension study; ii. all other participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) were treated with ligelizumab 120 mg liquid in vial s.c., Q4W, in a double-blind manner in this extension study; iii. participants transitioning from CQGE031C1301 (NCT03907878) and CQGE031C2202 (NCT03437278) were treated with ligelizumab 120 mg liquid in vial s.c., Q4W in an open-label manner in this extension study.

• After the first 12 weeks in TRT1 (and up to Week 52), all participants were switched to ligelizumab 120 mg s.c. pre-filled syringe (PFS) Q4W in an open-label manner and they were offered an opportunity to self-administer ligelizumab outside the clinic.

The second half of the treatment period (TRT2) was 52 weeks (from Week 52 to Week 104). Participants with UAS7>6 and <16 or with UAS7 ≥ 16 for whom the benefit-risk was deemed as positive by the investigator at Week 52 of TRT1 were transitioned to the TRT2 (ligelizumab 120 mg s.c. Q4W PFS) unless a decision to stop treatment was made based on a risk-benefit assessment. They were not allowed to discontinue H1- AH background medication.

Participants with UAS7 ≤ 6 at Week 52 of TRT1 entered the second (investigational treatment-free) observation period (OBS2) for up to 52 weeks and remained on the same H1-AH background medication they were taking in the preceding studies. Participants with UAS7 ≤ 6 at Week 52 of TRT1 who entered the second observation period (OBS2) and relapsed (UAS7 ≥ 16) were transitioned to the TRT2 and were also offered the opportunity to discontinue their H1-AH background medication (i.e. ligelizumab 120 mg s.c. q4w PFS monotherapy) after 12 weeks in TRT2. Participants who entered the OBS2 and did not relapse (UAS7<16) exited the study at the end of the OBS2 period.

Finally, participants who were in TRT2 entered the post-treatment follow-up period after treatment discontinuation, with duration of 12 weeks (for participants who did not complete a continuous 104-week treatment) or 52 weeks (for participants who completed the full 104-week treatment period without interruption). Participants who decided to remain on H1-AH background medication continued to use H1-AH background medication. Participants who decided to go off H1- AH background medication continued to remain off.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1033
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Written informed consent

• Subjects who successfully completed all of the treatment period and the follow-up period in any of the following studies: CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356), CQGE031C2202 (NCT03437278) or CQGE031C1301 (NCT03907878)

• Male and female, adult and adolescent subjects =12 years of age

• Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedule

Key Exclusion Criteria:

• Use of investigational drugs, other than those in use in the preceding studies, at the time of enrollment

• Use of omalizumab within 16 weeks of Screening

• History of hypersensitivity to the study drug ligelizumab or its components, or to drugs of similar chemical classes

• New onset or signs and symptoms of any form of chronic urticarias other than CSU during the preceding studies CQGE031C2302 (NCT03580369), CQGE031C2303 (NCT03580356) or CQGE031C2202 (NCT03437278).

• Diseases with possible symptoms of urticaria or angioedema

• Subjects with evidence of helminthic parasitic infection

• Documented history of anaphylaxis

• Pregnant or nursing (lactating) women

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• Ligelizumab
For the first 12 weeks of treatment: i) participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) previously treated with ligelizumab 72 mg LIVI s.c. Q4W were treated with the same dose regimen in a double-blind manner; ii) all other participants transitioning from CQGE031C2302 (NCT03580369) and CQGE031C2303 (NCT03580356) were treated with ligelizumab 120 mg LIVI s.c. Q4W in a double-blind manner; iii) participants transitioning from CQGE031C1301 (NCT03907878) and CQGE031C2202 (NCT03437278) were treated with ligelizumab 120 mg LIVI s.c. Q4W in an open-label manner. Thereafter, all participants were switched to ligelizumab 120 mg s.c. PFS Q4W in an open-label manner and they were offered an opportunity to self-administer ligelizumab. The longest possible treatment was 104 weeks, however this treatment might not be continuous and might span over a period of 156 weeks due to the possibility of entering the intervening observation period.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Bahia Blanca
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires	Nueve De Julio
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Capital Federal
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad de Mendoza	Mendoza
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Salta
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	East Melbourne	Victoria
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Jette	Brussel
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Loverval
Brazil	Novartis Investigative Site	Alphaville Barueri	Sao Paulo
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Santo Andre	SP
Brazil	Novartis Investigative Site	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Waterloo	Ontario
Chile	Novartis Investigative Site	Osorno
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Vitacura	Santiago
Colombia	Novartis Investigative Site	Medellin	Antioquia
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Olomouc
Czechia	Novartis Investigative Site	Plzen
Czechia	Novartis Investigative Site	Prague	Prague 1
Czechia	Novartis Investigative Site	Teplice	CZE
Denmark	Novartis Investigative Site	Copenhagen NV
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Clermont Ferrand
France	Novartis Investigative Site	Nice Cedex
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Toulouse
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Langenau
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Memmingen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Tuebingen
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Kecskemet	Bacs Kiskun
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged	Csongrad
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Belagavi	Karnataka
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Vijayawada
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Rehovot
Italy	Novartis Investigative Site	Cagliari	CA
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Siena	SI
Japan	Novartis Investigative Site	Chikushino	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Hiroshima City	Hiroshima
Japan	Novartis Investigative Site	Ichikawa	Chiba
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Izumo-city	Shimane
Japan	Novartis Investigative Site	Kamimashi-gun	Kumamoto
Japan	Novartis Investigative Site	Kawasaki	Kanagawa
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Machida-city	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Neyagawa	Osaka
Japan	Novartis Investigative Site	Nishinomiya-city	Hyogo
Japan	Novartis Investigative Site	Obihiro	Hokkaido
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Setagaya-ku	Tokyo
Japan	Novartis Investigative Site	Shinagawa ku	Tokyo
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Korea, Republic of	Novartis Investigative Site	Daegu	Dalseo Gu
Korea, Republic of	Novartis Investigative Site	Hwaseong si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Suwon si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Wonju	Gangwon-Do
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Malaysia	Novartis Investigative Site	Ipoh	Perak
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Penang
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Villahermosa	Tabasco
Netherlands	Novartis Investigative Site	Bergen op Zoom
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Utrecht
Oman	Novartis Investigative Site	Muscat
Peru	Novartis Investigative Site	Miraflores	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Philippines	Novartis Investigative Site	Pasig City
Philippines	Novartis Investigative Site	Taguig City	Metro Manila
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Ksawerow	POL
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Puerto Rico	Novartis Investigative Site	San Juan
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Cluj Napoca
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St.-Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Kezmarok
Slovakia	Novartis Investigative Site	Komarno
Slovakia	Novartis Investigative Site	Levice
Slovakia	Novartis Investigative Site	Nove Zamky
Slovakia	Novartis Investigative Site	Povazska Bystrica
Slovakia	Novartis Investigative Site	Svidnik
Slovakia	Novartis Investigative Site	Topolcany
Slovakia	Novartis Investigative Site	Zilina
South Africa	Novartis Investigative Site	Cape Town	Western Province
South Africa	Novartis Investigative Site	Cape Town
South Africa	Novartis Investigative Site	Durban
Spain	Novartis Investigative Site	Alcorcon	Madrid
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	Esplugues de Llobregat	Barcelona
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Tao Yuan
Thailand	Novartis Investigative Site	Bangkok	Phayathai
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Tunisia	Novartis Investigative Site	Sfax	Tunusia
Tunisia	Novartis Investigative Site	Sousse
Tunisia	Novartis Investigative Site	Tunis
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Denizli
Turkey	Novartis Investigative Site	Istanbul	Pendik
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Okmeydani
Turkey	Novartis Investigative Site	Samsun
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Bakersfield	California
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigative Site	Bellingham	Washington
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clackamas	Oregon
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	El Paso	Texas
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigative Site	Gilbert	Arizona
United States	Novartis Investigative Site	Greenacres City	Florida
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Litchfield Park	Arizona
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Missoula	Montana
United States	Novartis Investigative Site	Murray	Utah
United States	Novartis Investigative Site	North Charleston	South Carolina
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Redwood City	California
United States	Novartis Investigative Site	Rochester	Minnesota
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Jose	California
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Scottsdale	Arizona
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Toledo	Ohio
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	White Marsh	Maryland
United States	Novartis Investigative Site	Ypsilanti	Michigan
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Guatemala,  Hungary,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Malaysia,  Mexico,  Netherlands,  Oman,  Peru,  Philippines,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Slovakia,  South Africa,  Spain,  Taiwan,  Thailand,  Tunisia,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Well-controlled Disease (UAS7 = 6) at Week 12	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The percentage of subjects transitioning from CQGE031C2302 and CQGE031C2303 and receiving the same dose regimen as in the core studies with UAS7= 6 at Week 12 was estimated using multiple imputation method. The 95% confidence interval was derived based on the Wilson score method with continuity correction.	Week 12 of the extension study
Primary	Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in Core Studies and Who Achieved UAS7= 6 at Week 12 in Core Studies, With Well-controlled Disease (UAS7 = 6) at Week 12 of the Extension Study	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals and the intensity of the pruritus over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the UAS7 was missing for that week. Missing data was considered as non-responder.; The percentage of subjects transitioning from core studies (CQGE031C2302 and CQGE031C2303) and receiving the same dose regimen as in the core studies who achieved UAS7 = 6 at week 12 in the core studies with UAS7= 6 at Week 12 of the extension study was estimated based on observed data.	Week 12 of the extension study
Secondary	Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With Completely Controlled Disease (UAS7 =0) at Week 12	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The percentage of subjects transitioning from core studies (CQGE031C2302 and CQGE031C2303) and receiving the same dose regimen as in the core studies with UAS7 = 0 at Week 12 was estimated using multiple imputation method.	Week 12 of the extension study
Secondary	Change From Extension Study Baseline in the UAS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity. A negative change score from extension study baseline indicates improvement.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week.; The absolute change from extension study baseline in the UAS7 at Week 12 was estimated using multiple imputation method.	Extension study baseline (Week 0), Week 12 of the extension study
Secondary	Change From Extension Study Baseline in the ISS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies	The Itch Severity Score (ISS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (intense/severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 preceding days. The ISS7 ranged from 0 to 21. A higher ISS7 indicated more severe itching. A negative change score from baseline indicates improvement.; A minimum of 4 out of 7 daily scores were needed to calculate the ISS7 values. Otherwise, the weekly score was missing for that week.; The absolute change from extension study baseline in the ISS7 at Week 12 in all subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies was estimated using multiple imputation method.	Extension study baseline (Week 0), Week 12 of the extension study
Secondary	Change From Extension Study Baseline in the HSS7 at Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies	The Hive Severity Score (HSS) was recorded by the subject twice daily in their eDiary, on a scale of 0 (none) to 3 (> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 preceding days. The HSS7 ranged from 0 to 21 A higher HSS7 indicated a greater number of hives. A negative change score from baseline indicates improvement.; A minimum of 4 out of 7 daily scores were needed to calculate the HSS7 values. Otherwise, the weekly score was missing for that week.; The absolute change from extension study baseline in the HSS7 at Week 12 in all subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies was estimated using multiple imputation method.	Extension study baseline (Week 0), Week 12 of the extension study
Secondary	Cumulative Number of Angioedema-free Weeks (AAS7=0) up to Week 12 in All Subjects From Core Studies (CQGE031C2302 and CQGE031C2303) Receiving the Same Dose Regimen as in the Core Studies	The Weekly angioedema activity score (AAS) is a validated tool to assess occurrence of episodes of angioedema. If the subject reported the occurrence of angioedema ("opening question") with "no", AAS score for this day was 0. If "yes" was the answer to the opening question, the subject continued to answer questions about the duration, severity and impact on daily functioning and appearance of the angioedema. A score between 0 and 3 was assigned to every answer field. The AAS7 was the weekly sum of the daily AAS. AAS7 scores ranged from 0-105. Higher score indicated more severe disease.; AAS7 in all subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies was estimated using multiple imputation method. The imputed AAS7 = 0 was used for the cumulative number of weeks that subjects achieved AAS7 = 0 response calculation	From extension study baseline (Week 0) up to Week 12 of the extension study
Secondary	Percentage of Subjects From Core Studies (CQGE031C2302 and CQGE031C2303), Receiving the Same Dose Regimen as in the Core Studies, With DLQI = 0-1 at Week 12	The Dermatology Life Quality Index (DLQI) is a 10-item dermatology-specific quality of life (QoL) measure. Subjects rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives thinking about the previous 7 days. An overall score was calculated and ranged from 0 to 30. Higher scores indicated worse disease-related QoL. A DLQI score of 0 or 1 indicated that there was no impact of a skin disease on the patient's life.; The percentage of subjects from core studies (CQGE031C2302 and CQGE031C2303) receiving the same dose regimen as in the core studies with DLQI = 0-1 at Week 12 was estimated using multiple imputation method.	Week 12 of the extension study
Secondary	Percentage of Subjects With Well-controlled Disease (UAS7 = 6) 12 Weeks After Starting Self-administration	The Urticaria Activity Score (UAS) is a composite, diary-recorded score with numeric severity intensity ratings (0=none to 3=intense/severe) for the number of wheals (hives) and the intensity of the pruritus (itch) over the past 12 hours (twice daily). The daily UAS is calculated as the average of the morning and evening scores. The UAS7 is the weekly sum of the daily UAS, which is the composite score of the intensity of pruritus and the number of wheals. UAS7 scores ranged from 0 to 42. A higher UAS7 indicated greater urticaria disease activity.; A minimum of 4 out of 7 daily scores were needed to calculate the UAS7 values. Otherwise, the weekly score was missing for that week. Missing data was considered as non-responder in the analysis.; The percentage of subjects with UAS7= 6 at Week 24 (i.e., 12 weeks after starting self-administration) was estimated based on observed data.	Week 24 of the extension study

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