A Phase III Study of 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 Efficacy and Safety of Ligelizumab (QGE031) in the Treatment of Chronic Spontaneous Urticaria (CSU) in Adolescents and Adults Inadequately Controlled With H1-antihistamines
2 other identifiers
interventional
1,078
26 countries
172
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.
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
172 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
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 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 22, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
June 14, 2022
CompletedResults Posted
Study results publicly available
March 25, 2024
CompletedJanuary 7, 2025
January 1, 2025
2.7 years
June 26, 2018
December 14, 2022
January 6, 2025
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 Percentage 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 Percentage of Participants With DLQI Score of 0 - 1 at Week 12 (Multiple Imputation - Adults, Observed Data for Adolescents)
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 (183)
Allervie Clinical Research
Birmingham, Alabama, 35209, United States
Medical Resch of Arizona-Div of Allergy Asthma and Immunology
Scottsdale, Arizona, 85251, United States
Atria Clinical Research Asthma and Allergy Institute
Little Rock, Arkansas, 72209, United States
DeMera Allergy Asthma and Immun Ctr
Fresno, California, 93720, United States
California Allergy and Asthma Medical Group
Los Angeles, California, 90025, United States
Jonathan Corren Inc
Los Angeles, California, 90025, United States
Allergy and Asthma Consultants
Redwood City, California, 94063, United States
Allergy and Asthma Associates of Santa Clara Vally Center
San Jose, California, 95117, United States
Sarasota Clinical Research
Sarasota, Florida, 34233, United States
Olympian Clinical Research
Tampa, Florida, 33609, United States
Idaho Research
Eagle, Idaho, 83616, United States
Midwest Allergy Sinus Asthma SC
Normal, Illinois, 61761, United States
John Hopkins University
Baltimore, Maryland, 21204, United States
Institute for Asthma and Allergy PC
Chevy Chase, Maryland, 20815, United States
Chesapeake Clinical Research
White Marsh, Maryland, 21162, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Midwest Clinical Research LcLC
St Louis, Missouri, 63141, United States
Montana Medical Research
Missoula, Montana, 59808, United States
The Asthma and Allergy Center PC
Papillion, Nebraska, 68046, United States
Icahn School Of Med At Mount Sinai
New York, New York, 10029, United States
Toledo Institute of Clinical Research
Toledo, Ohio, 43617, United States
Allergy Asthma and Clinical Research
Oklahoma City, Oklahoma, 73120, United States
PCR DBA Columbia Asthma and Allergy
Clackamas, Oregon, 97015, United States
Allergy and Asthma Specialists PC
Blue Bell, Pennsylvania, 19422, United States
Allergy and Clinical Immunology Associates
Pittsburgh, Pennsylvania, 15241, United States
National Allergy and Asthma Research LLS
North Charleston, South Carolina, 29420, United States
Bellaire Dermatology Associates
Bellaire, Texas, 77401, United States
Western Sky Medical Research
El Paso, Texas, 79924, United States
North Texas Inst For Clinical Tri
Fort Worth, Texas, 76132, United States
Allergy and Asthma Research Center PA
San Antonio, Texas, 78229, United States
Quality Assurance Research Center
San Antonio, Texas, 78230, United States
Allergy and Asthma Care of Waco
Waco, Texas, 76712, United States
Allergy Associates of Utah
Sandy City, Utah, 84093, United States
Bellingham Asthma Allergy and Immunology
Bellingham, Washington, 98225, United States
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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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
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 20, 2018
Primary Completion
June 22, 2021
Study Completion
June 14, 2022
Last Updated
January 7, 2025
Results First Posted
March 25, 2024
Record last verified: 2025-01
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