A Phase III Study of Safety 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 Safety and Efficacy 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: NCT03580369
• Other study ID #: CQGE031C2302
• Secondary ID: 2018-000839-28
• Status: Completed
• Phase: Phase 3
• Start date: October 17, 2018
• Est. completion date: June 14, 2022

Study information

• Verified date: July 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to establish safety and efficacy of ligelizumab in adolescent and adult subjects with Chronic Spontaneous Urticaria (CSU) who remain symptomatic despite standard of care treatment by demonstrating better efficacy over omalizumab and over placebo.

The study population consisted of 1,072 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: 1072
• Est. completion date: June 14, 2022
• Est. primary completion date: July 16, 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	Bahia Blanca
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	Capital Federal
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Wien
Brazil	Novartis Investigative Site	Alphaville Barueri	Sao Paulo
Brazil	Novartis Investigative Site	Santo Andre	SP
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Vitoria	ES
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	Mississauga	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Waterloo	Ontario
Colombia	Novartis Investigative Site	Bogota
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
Denmark	Novartis Investigative Site	Herlev
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Pierre Benite Cedex
France	Novartis Investigative Site	Toulouse
France	Novartis Investigative Site	Trevenans
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Langenau
Germany	Novartis Investigative Site	Mainz
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Memmingen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Oldenburg
Greece	Novartis Investigative Site	Athens	GR
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	Belagavi	Karnataka
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Nashik	Maharashtra
India	Novartis Investigative Site	Navi Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Vijayawada
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
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, 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
Malaysia	Novartis Investigative Site	Ipoh	Perak
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Penang
Oman	Novartis Investigative Site	Muscat
Peru	Novartis Investigative Site	Miraflores	Lima
Peru	Novartis Investigative Site	San Borja	Lima
Poland	Novartis Investigative Site	Kielce
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Ksawerow	POL
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Wroclaw
Puerto Rico	Novartis Investigative Site	San Juan
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	Saratov
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St. Petersburg
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
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	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	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Sweden	Novartis Investigative Site	Malmo
Thailand	Novartis Investigative Site	Bangkok	Phayathai
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkoknoi	Bangkok
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigative Site	Denizli
Turkey	Novartis Investigative Site	Gaziantep
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 States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Bakersfield	California
United States	Novartis Investigative Site	Bangor	Maine
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clarkston	Michigan
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Denver	Colorado
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	Huntington Beach	California
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	Long Beach	California
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Pflugerville	Texas
United States	Novartis Investigative Site	Plymouth	Minnesota
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Scottsdale	Arizona
United States	Novartis Investigative Site	South Burlington	Vermont
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Waldorf	Maryland
United States	Novartis Investigative Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Bulgaria,  Canada,  Colombia,  Croatia,  Czechia,  Denmark,  France,  Germany,  Greece,  Guatemala,  Hungary,  India,  Korea, Republic of,  Malaysia,  Oman,  Peru,  Poland,  Puerto Rico,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Thailand,  Turkey, 

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 Proportion 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.; 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 Proportion 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, meaning, 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).; No statistical anaylsis was planned for adolescent group.	Baseline, 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

External Links

•   A Plain Language Trial Summary is available on novctrd.com.