A Phase III Study of and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines.

Chronic Spontaneous Urticaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03580356
• Other study ID #: CQGE031C2303
• Secondary ID: 2018-000840-24
• Status: Completed
• Phase: Phase 3
• Start date: October 20, 2018
• Est. completion date: June 14, 2022

Study information

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

Clinical Trial Summary

The purpose of this study was to establish efficacy and safety of ligelizumab in adolescent and adult subjects with CSU who remained symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo. The study population consisted of 1,079 male and female subjects aged ≥ 12 years who were diagnosed with CSU and who remained symptomatic despite the use of H1-antihistamines. This was a multi-center, randomized, double-blind, active- and placebo-controlled, parallel-group study. There was a screening period of up to 28 days, a 52 week double-blind treatment period, and a 12 week post-treatment follow-up period.

Description:

This was a Phase III multi-center, randomized, double-blind, active and placebo-controlled, parallel-group study. The study consisted of 3 distinct periods: - Screening period (Day -28 to Day 1): Duration of up to 4 weeks in which subjects who have given informed consent were assessed for eligibility. - Double-blind treatment period (52 weeks): The subjects were seen in the clinic every 4 weeks. - Post-treatment follow-up period (12 weeks): This period consists of 3 visits (every 4 weeks) with the final visit occurring 16 weeks after the last dose at Week 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1078
• Est. completion date: June 14, 2022
• Est. primary completion date: June 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Key Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study. The subject's, parent's or legal guardian's signed written informed consent and child's assent, if appropriate, must be obtained before any assessment is performed. Of note, if the subject reaches age of consent (age as per local law) during the study, they will also need to sign the corresponding study Informed Consent Form (ICF) at the next study visit.
• Male and female subjects = 12 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 randomization,

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-antihistamine
• UAS7 score (range 0-42) = 16 and HSS7 (range 0-21) = 8 during the 7 days prior to randomization (Visit 110, Day 1)
• Subjects must be on H1-antihistamine at only locally label approved doses for treatment of CSU starting at Visit 1 (Day -28 to Day -14)
• Willing and able to complete a daily symptom 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 drugs or their excipients or to drugs of similar chemical classes (i.e. to murine, chimeric or human antibodies).
• Subjects having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), 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 (eg, 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 be randomized and will not be allowed to rescreen.
• Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
• Prior exposure to ligelizumab or omalizumab.
• H1-AH used as background medication at greater than locally label-approved doses after visit 1

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Biological:
• Ligelizumab
Liquid in vial
• Omalizumab
Lyophilized powder for solution in vial

Other:
• Placebo
Liquid in vial

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad de Mendoza	Mendoza
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
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Bruxelles
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	Sao Jose do Rio Preto	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Chile	Novartis Investigative Site	Osorno
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Vitacura	Santiago
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Clermont Ferrand
France	Novartis Investigative Site	La Tronche
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Rouen
Germany	Novartis Investigative Site	Bad Bentheim
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Gottingen
Germany	Novartis Investigative Site	Halle
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Quedlinburg
Germany	Novartis Investigative Site	Simmern
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Tuebingen
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
Israel	Novartis Investigative Site	Afula
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	Catania	CT
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Siena	SI
Japan	Novartis Investigative Site	Amagasaki city	Hyogo
Japan	Novartis Investigative Site	Chikushino	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Hiroshima
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	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
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Villahermosa	Tabasco
Netherlands	Novartis Investigative Site	Bergen op Zoom
Netherlands	Novartis Investigative Site	Breda	CK
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Utrecht
Philippines	Novartis Investigative Site	Lipa City	Batangas
Philippines	Novartis Investigative Site	Makati City
Philippines	Novartis Investigative Site	Pasig City
Philippines	Novartis Investigative Site	Quezon
Philippines	Novartis Investigative Site	Taguig City	Metro Manila
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krosno
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Ossy
Poland	Novartis Investigative Site	Sopot
Poland	Novartis Investigative Site	Warszawa
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest	District 2
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Iasi
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St.-Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Slovakia	Novartis Investigative Site	Kezmarok
Slovakia	Novartis Investigative Site	Komarno
Slovakia	Novartis Investigative Site	Levice	Slovak Republic
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
Spain	Novartis Investigative Site	Alcorcon	Madrid
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Granada
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	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Tao Yuan
Tunisia	Novartis Investigative Site	Sfax	Tunusia
Tunisia	Novartis Investigative Site	Sousse
Tunisia	Novartis Investigative Site	Tunis
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bellaire	Texas
United States	Novartis Investigative Site	Bellingham	Washington
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Blue Bell	Pennsylvania
United States	Novartis Investigative Site	Chevy Chase	Maryland
United States	Novartis Investigative Site	Clackamas	Oregon
United States	Novartis Investigative Site	Eagle	Idaho
United States	Novartis Investigative Site	El Paso	Texas
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Fresno	California
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Missoula	Montana
United States	Novartis Investigative Site	Murray	Utah
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Normal	Illinois
United States	Novartis Investigative Site	North Charleston	South Carolina
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Papillion	Nebraska
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 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	Tampa	Florida
United States	Novartis Investigative Site	Toledo	Ohio
United States	Novartis Investigative Site	Waco	Texas
United States	Novartis Investigative Site	White Marsh	Maryland
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,  Belgium,  Brazil,  Chile,  Estonia,  Finland,  France,  Germany,  India,  Israel,  Italy,  Japan,  Lebanon,  Mexico,  Netherlands,  Philippines,  Poland,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan,  Tunisia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects	The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. 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). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of 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). Negative change from baseline indicates improvement	Baseline, Week 12
Primary	Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS)	The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. 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). Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of 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). Negative change from baseline indicates improvement	Baseline, Week 12
Secondary	Number and Percentage of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)	The Urticaria Activity Score (UAS) is the sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is the sum of the HSS7 and the ISS7 scores. The possible range of the weekly UAS7 score is 0 to 42. Complete UAS7 response is defined as UAS7 = 0. Data is presented as percentage of patients with a UAS7=0 score. No Statistical analysis was planned for adolescent group.	Week 12
Secondary	Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS)	Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at 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) Negative change from baseline indicates improvement.	Baseline, Week 12
Secondary	Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS)	Improvement of severity of itch assessed as absolute change from baseline in ISS7 score at 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) Negative change from baseline indicates improvement.. No Statistical Analysis was planned for adolescent population.	Baseline, Week 12
Secondary	Number and Percentage of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)	Assessed as percentage of subjects achieving DLQI = 0-1, which means No impact on subjects quality of life at Week 12 The Dermatology life Quality Index (DLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). Data is presented as percentage of patients with a DLQI=0 score. No statistical analysis was planned for adolescent group.	Week 12
Secondary	Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS)	Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity.	Baseline, Week 12
Secondary	Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS)	Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-15 (mean day sum score) where higher scores indicate increased angioedema activity. No Statistical Analysis was planned.	Baseline, Week 12