Clinical trial NCT03580356: A Phase III Study of and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Spontaneous Urticaria
Keywords: Anti-IgE
CSU
Chronic Spontaneous Urticaria
hives severity score
itch severity score
urticaria activity score
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-07-09
Enrollment: 1078
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This was a Phase III 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.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline in UAS7 at Week 12 (Multiple Imputation) of Adult Subjects
timeFrame: Baseline, Week 12
measure: Mean Change From Baseline in UAS7 at Week 12 (Observed Data) of Adolescent Subjects (FAS)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Number and Percentage of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
timeFrame: Week 12
measure: Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS)
timeFrame: Baseline, Week 12
measure: Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS)
timeFrame: Baseline, Week 12
measure: Number and Percentage of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
timeFrame: Week 12
measure: Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS)
timeFrame: Baseline, Week 12
measure: Cumulative Number of Weeks of AAS7=0 up to Week 12 (Observed Data) of Adolescent Subjects (FAS)
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allervie Clinical Research
state: Alabama
city: Scottsdale
country: United States
facility: Medical Resch of Arizona-Div of Allergy Asthma and Immunology
state: Arizona
city: Little Rock
country: United States
facility: Atria Clinical Research Asthma and Allergy Institute
state: Arkansas
city: Fresno
country: United States
facility: DeMera Allergy Asthma and Immun Ctr
state: California
city: Los Angeles
country: United States
facility: California Allergy and Asthma Medical Group
state: California
city: Los Angeles
country: United States
facility: Jonathan Corren Inc
state: California
city: Redwood City
country: United States
facility: Allergy and Asthma Consultants
state: California
city: San Jose
country: United States
facility: Allergy and Asthma Associates of Santa Clara Vally Center
state: California
city: Sarasota
country: United States
facility: Sarasota Clinical Research
state: Florida
city: Tampa
country: United States
facility: Olympian Clinical Research
state: Florida
city: Eagle
country: United States
facility: Idaho Research
state: Idaho
city: Normal
country: United States
facility: Midwest Allergy Sinus Asthma SC
state: Illinois
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Chevy Chase
country: United States
facility: Institute for Asthma and Allergy PC
state: Maryland
city: White Marsh
country: United States
facility: Chesapeake Clinical Research
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Midwest Clinical Research LcLC
state: Missouri
city: Missoula
country: United States
facility: Montana Medical Research
state: Montana
city: Papillion
country: United States
facility: The Asthma and Allergy Center PC
state: Nebraska
city: New York
country: United States
facility: Icahn School Of Med At Mount Sinai
state: New York
city: Toledo
country: United States
facility: Toledo Institute of Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Allergy Asthma and Clinical Research
state: Oklahoma
city: Clackamas
country: United States
facility: PCR DBA Columbia Asthma and Allergy
state: Oregon
city: Blue Bell
country: United States
facility: Allergy and Asthma Specialists PC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: North Charleston
country: United States
facility: National Allergy and Asthma Research LLS
state: South Carolina
city: Bellaire
country: United States
facility: Bellaire Dermatology Associates
state: Texas
city: El Paso
country: United States
facility: Western Sky Medical Research
state: Texas
city: Fort Worth
country: United States
facility: North Texas Inst For Clinical Tri
state: Texas
city: San Antonio
country: United States
facility: Allergy and Asthma Research Center PA
state: Texas
city: San Antonio
country: United States
facility: Quality Assurance Research Center
state: Texas
city: Waco
country: United States
facility: Allergy and Asthma Care of Waco
state: Texas
city: Sandy
country: United States
facility: Allergy Associates of Utah
state: Utah
city: Bellingham
country: United States
facility: Bellingham Asthma Allergy and Immunology
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad de Mendoza
country: Argentina
facility: Novartis Investigative Site
state: Mendoza
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
state: Rosario
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Caba
country: Argentina
facility: Novartis Investigative Site
city: Salta
country: Argentina
facility: Novartis Investigative Site
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Loverval
country: Belgium
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: Alphaville Barueri
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vitacura
country: Chile
facility: Novartis Investigative Site
state: Santiago
city: Osorno
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Clermont Ferrand
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Bad Bentheim
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Gera
country: Germany
facility: Novartis Investigative Site
city: Gottingen
country: Germany
facility: Novartis Investigative Site
city: Halle S
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Osnabrueck
country: Germany
facility: Novartis Investigative Site
city: Quedlinburg
country: Germany
facility: Novartis Investigative Site
city: Simmern
country: Germany
facility: Novartis Investigative Site
city: Stade
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Mangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Bikaner
country: India
facility: Novartis Investigative Site
state: Rajasthan
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Rehovot
country: Israel
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Chikushino
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Amagasaki city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kawasaki
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kamimashi-gun
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Sakai
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Izumo-city
country: Japan
facility: Novartis Investigative Site
state: Shimane
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Machida
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Hiroshima
country: Japan
facility: Novartis Investigative Site
city: Kobe-shi
country: Japan
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Villahermosa
country: Mexico
facility: Novartis Investigative Site
state: Tabasco
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Amersfroort
country: Netherlands
facility: Novartis Investigative Site
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Lipa City
country: Philippines
facility: Novartis Investigative Site
state: Batangas
city: Taguig City
country: Philippines
facility: Novartis Investigative Site
state: Metro Manila
city: Makati City
country: Philippines
facility: Novartis Investigative Site
city: Pasig City
country: Philippines
facility: Novartis Investigative Site
city: Quezon
country: Philippines
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Krosno
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Ossy
country: Poland
facility: Novartis Investigative Site
city: Sopot
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
state: District 2
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Craiova
country: Romania
facility: Novartis Investigative Site
city: Iasi
country: Romania
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Stavropol
country: Russian Federation
facility: Novartis Investigative Site
city: Kezmarok
country: Slovakia
facility: Novartis Investigative Site
city: Komarno
country: Slovakia
facility: Novartis Investigative Site
city: Levice
country: Slovakia
facility: Novartis Investigative Site
city: Nove Zamky
country: Slovakia
facility: Novartis Investigative Site
city: Povazska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Svidnik
country: Slovakia
facility: Novartis Investigative Site
city: Topolcany
country: Slovakia
facility: Novartis Investigative Site
city: Zilina
country: Slovakia
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Alcorcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Tunis
country: Tunisia
facility: Novartis Investigative Site
state: Tunisie
city: Sfax
country: Tunisia
facility: Novartis Investigative Site
state: Tunusia
city: Sousse
country: Tunisia
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: