A Phase III Study of Safety and Efficacy of Ligelizumab in the Treatment of CSU in Adolescents and Adults Inadequately Controlled With H1-antihistamines
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
2 other identifiers
interventional
1,072
29 countries
161
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2018
Typical duration for phase_3
161 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2018
CompletedFirst Posted
Study publicly available on registry
July 9, 2018
CompletedStudy Start
First participant enrolled
October 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 16, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 14, 2022
CompletedResults Posted
Study results publicly available
December 30, 2022
CompletedJuly 24, 2023
July 1, 2023
2.7 years
June 26, 2018
November 30, 2022
July 20, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (6)
Number and Proportion of Subjects With UAS7=0 Response at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
Week 12
Mean Change From Baseline in ISS7 at Week 12 (Multiple Imputation) of Adult Subjects (FAS)
Baseline, Week 12
Mean Change From Baseline in ISS7 at Week 12 (Observed Data) of Adolescent Subjects, (FAS)
Baseline, Week 12
Number and Proportion of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
Baseline, Week 12
Cumulative Number of Weeks of AAS7=0 up to Week 12 (Multiple Imputation) of Adult Subjects (FAS)
Baseline, Week 12
- +1 more secondary outcomes
Study Arms (4)
Ligelizumab 120 mg
EXPERIMENTALLigelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w
Ligelizumab 72 mg
EXPERIMENTALLigelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w
Omalizumab 300 mg
ACTIVE COMPARATOROmalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w
Placebo
PLACEBO COMPARATORPlacebo-ligelizumab arm: 2 injections of 1.0mL of ligelizumab placebo from Week 0 through Week 20; 1 injection of 1.0mL of ligelizumab 120 mg + 1 injection of 1.0 mL ligelizumab placebo from Week 24 through Week 48
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (161)
Novartis Investigative Site
Gilbert, Arizona, 85234, United States
Novartis Investigative Site
Litchfield Park, Arizona, 85340, United States
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Scottsdale, Arizona, 85258, United States
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Little Rock, Arkansas, 72205, United States
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Bakersfield, California, 93301, United States
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Huntington Beach, California, 92647, United States
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Long Beach, California, 90808, United States
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Colorado Springs, Colorado, 80907, United States
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Denver, Colorado, 80230, United States
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Greenacres City, Florida, 33467, United States
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Tallahassee, Florida, 32308, United States
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Tampa, Florida, 33613, United States
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Boise, Idaho, 83706, United States
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Evansville, Indiana, 47713, United States
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Indianapolis, Indiana, 46256, United States
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Overland Park, Kansas, 66211, United States
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Bangor, Maine, 04401, United States
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Waldorf, Maryland, 20602, United States
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Clarkston, Michigan, 48346, United States
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Ypsilanti, Michigan, 48197, United States
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Plymouth, Minnesota, 55441, United States
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Asheville, North Carolina, 28801, United States
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Cincinnati, Ohio, 45231, United States
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Tulsa, Oklahoma, 74136, United States
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Medford, Oregon, 97504, United States
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Dallas, Texas, 75230, United States
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Dallas, Texas, 75231, United States
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Pflugerville, Texas, 78660, United States
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San Antonio, Texas, 78229, United States
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South Burlington, Vermont, 05403, United States
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CABA, Buenos Aires, C1056ABJ, Argentina
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CABA, Buenos Aires, C1414AIF, Argentina
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Ciudad Autonoma de Bs As, Buenos Aires, C1425BEA, Argentina
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La Plata, Buenos Aires, B1902COS, Argentina
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Buenos Aires, Nueve De Julio, B6500BWQ, Argentina
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Bahía Blanca, B8000JRB, Argentina
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Buenos Aires, C1125ABE, Argentina
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Capital Federal, C1023AAB, Argentina
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Innsbruck, 6020, Austria
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Vienna, A 1090, Austria
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Vitória, Espírito Santo, 29025 023, Brazil
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Alphaville Barueri, São Paulo, 06454010, Brazil
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Santo André, São Paulo, 09060 650, Brazil
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São Paulo, São Paulo, 05403 000, Brazil
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Pleven, 5800, Bulgaria
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Sofia, 1407, Bulgaria
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Sofia, 1431, Bulgaria
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Sofia, 1606, Bulgaria
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Varna, 9000, Bulgaria
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Hamilton, Ontario, L8N 3Z5, Canada
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Kingston, Ontario, K7L 2V7, Canada
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Mississauga, Ontario, L5A 3V4, Canada
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Toronto, Ontario, M3B 3S6, Canada
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Waterloo, Ontario, N2J 1C4, Canada
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Montreal, Quebec, H2V 2K1, Canada
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Québec, Quebec, G1V 4W2, Canada
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Medellín, Antioquia, 0050010, Colombia
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Bogotá, 110221, Colombia
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Zagreb, 10000, Croatia
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Teplice, CZE, 415 01, Czechia
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Prague, Prague 1, 11000, Czechia
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Olomouc, 775 20, Czechia
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Pilsen, 305 99, Czechia
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Copenhagen NV, 2400, Denmark
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Herlev, 2730, Denmark
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Bordeaux, 33075, France
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Montpellier, 34295, France
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Pierre-Bénite, 69495, France
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Toulouse, 31400, France
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Trévenans, 90400, France
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Berlin, 13353, Germany
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Bochum, 44791, Germany
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Bochum, 44793, Germany
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Erlangen, 91054, Germany
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Essen, 45147, Germany
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Freiburg im Breisgau, 79106, Germany
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Jena, 07740, Germany
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Langenau, 89129, Germany
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Mainz, 55131, Germany
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Marburg, 35039, Germany
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Memmingen, 87700, Germany
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München, 81377, Germany
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Oldenburg, 26133, Germany
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Athens, GR, 115 27, Greece
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Athens, 115 27, Greece
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Athens, 12462, Greece
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Athens, 161 21, Greece
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Guatemala City, 01010, Guatemala
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Guatemala City, 1015, Guatemala
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Kecskemét, Bács-Kiskun county, 6000, Hungary
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Szeged, Csongrád megye, 6720, Hungary
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Debrecen, 4032, Hungary
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Pécs, 7623, Hungary
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Belagavi, Karnataka, 590010, India
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Nashik, Maharashtra, 422 101, India
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Nashik, Maharashtra, 422005, India
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Navi Mumbai, Maharashtra, 400 706, India
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New Delhi, 110029, India
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Vijayawada, 520002, India
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Kuala Lumpur, Kuala Lumpur, 50586, Malaysia
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Ipoh, Perak, 30450, Malaysia
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George Town, Pulau Pinang, 10990, Malaysia
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Muscat, 123, Oman
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Miraflores, Lima region, 15074, Peru
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San Borja, Lima region, 41, Peru
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Ksawerów, POL, 95-054, Poland
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Kielce, 25-155, Poland
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Krakow, 31-530, Poland
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Lublin, 20-080, Poland
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Rzeszów, 35 055, Poland
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Wroclaw, 50 566, Poland
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San Juan, 00927, Puerto Rico
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Moscow, 123182, Russia
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Rostov-on-Don, 344022, Russia
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Ryazan, 390046, Russia
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Saint Petersburg, 193231, Russia
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Saint Petersburg, 194354, Russia
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Saratov, 410012, Russia
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Smolensk, 214019, Russia
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Singapore, 119074, Singapore
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Singapore, 169608, Singapore
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Singapore, 229899, Singapore
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Singapore, 308205, Singapore
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Cape Town, Western Province, 7700, South Africa
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Cape Town, 7700, South Africa
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Durban, 3630, South Africa
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Daegu, Dalseo Gu, 42602, South Korea
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Wŏnju, Gangwon-do, 26426, South Korea
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Bundang Gu, Gyeonggi-do, 13620, South Korea
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Hwaseong-si, Gyeonggi-do, 18450, South Korea
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Suwon, Gyeonggi-do, 16499, South Korea
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Seoul, Korea, 08308, South Korea
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Seoul, Seocho Gu, 06591, South Korea
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Incheon, 405 760, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06973, South Korea
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Seoul, 07061, South Korea
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Seoul, 150-950, South Korea
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Málaga, Andalusia, 29009, Spain
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Seville, Andalusia, 41009, Spain
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Bilbao, Basque Country, 48013, Spain
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Barcelona, Catalonia, 08003, Spain
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Barcelona, Catalonia, 08035, Spain
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Barcelona, Catalonia, 08036, Spain
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Alicante, Valencia, 03010, Spain
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Barcelona, 08041, Spain
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Malmo, SE-205 02, Sweden
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Bangkoknoi, Bangkok, 10700, Thailand
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Bangkok, Phayathai, 10400, Thailand
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Bangkok, 10400, Thailand
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Istanbul, Pendik, 348999, Turkey (Türkiye)
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Istanbul, TUR, 34098, Turkey (Türkiye)
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Aydin, 09100, Turkey (Türkiye)
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Denizli, 20070, Turkey (Türkiye)
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Gaziantep, 27310, Turkey (Türkiye)
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Izmir, 35380, Turkey (Türkiye)
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Okmeydanı, 34370, Turkey (Türkiye)
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Samsun, 55139, Turkey (Türkiye)
Related Publications (1)
Maurer M, Ensina LF, Gimenez-Arnau AM, Sussman G, Hide M, Saini S, Grattan C, Fomina D, Rigopoulos D, Berard F, Canonica GW, Rockmann H, Irani C, Szepietowski JC, Leflein J, Bernstein JA, Peter JG, Kulthanan K, Godse K, Ardusso L, Ukhanova O, Staubach P, Sinclair R, Gogate S, Thomsen SF, Tanus T, Ye YM, Burciu A, Barve A, Modi D, Scosyrev E, Hua E, Letzelter K, Varanasi V, Patekar M, Severin T; PEARL-1 and PEARL-2 trial investigators. Efficacy and safety of ligelizumab in adults and adolescents with chronic spontaneous urticaria: results of two phase 3 randomised controlled trials. Lancet. 2024 Jan 13;403(10422):147-159. doi: 10.1016/S0140-6736(23)01684-7. Epub 2023 Nov 23.
PMID: 38008109DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The difference of 4 subjects between RAN (1034) vs FAS (1030) is due to mis-randomization of 4 subjects. These subjects did not receive Ligelizumab and hence rightfully not included in FAS (though included in RAN).
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Patients, investigator staff and personnel performing the study assessments remained blinded to the identity of the treatment from the time of randomization until final database lock. The study drug was prepared by an independent unblinded pharmacist (or authorized delegate) and administered by an independent unblinded study drug administrator. Neither the unblinded pharmacist nor the unblinded study drug administrator was involved in any assessments.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2018
First Posted
July 9, 2018
Study Start
October 17, 2018
Primary Completion
July 16, 2021
Study Completion
June 14, 2022
Last Updated
July 24, 2023
Results First Posted
December 30, 2022
Record last verified: 2023-07
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com