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

NCT ID: NCT03580356

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1078 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-20
• Study Completion Date: 2022-06-14

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.

Conditions

Chronic Spontaneous Urticaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ligelizumab 120 mg

Ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Group Type: EXPERIMENTAL

Ligelizumab

Intervention Type: BIOLOGICAL

Liquid in vial

Ligelizumab 72 mg

Ligelizumab 72 mg arm: 1 injection of 0.6 mL ligelizumab + 1 injection of 1.0 mL ligelizumab placebo q4w

Group Type: EXPERIMENTAL

Ligelizumab

Intervention Type: BIOLOGICAL

Liquid in vial

Omalizumab 300 mg

Omalizumab 300 mg arm: 2 injections of 1.2 mL omalizumab q4w

Group Type: ACTIVE_COMPARATOR

Omalizumab

Intervention Type: BIOLOGICAL

Lyophilized powder for solution in vial

Placebo

Placebo-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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Liquid in vial

Interventions

Ligelizumab

Liquid in vial

Intervention Type: BIOLOGICAL

Omalizumab

Lyophilized powder for solution in vial

Intervention Type: BIOLOGICAL

Placebo

Liquid in vial

Intervention Type: OTHER

Eligibility Criteria

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.

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Allervie Clinical Research

Birmingham, Alabama, United States

Medical Resch of Arizona-Div of Allergy Asthma and Immunology

Scottsdale, Arizona, United States

Atria Clinical Research Asthma and Allergy Institute

Little Rock, Arkansas, United States

DeMera Allergy Asthma and Immun Ctr

Fresno, California, United States

California Allergy and Asthma Medical Group

Los Angeles, California, United States

Jonathan Corren Inc

Los Angeles, California, United States

Allergy and Asthma Consultants

Redwood City, California, United States

Allergy and Asthma Associates of Santa Clara Vally Center

San Jose, California, United States

Sarasota Clinical Research

Sarasota, Florida, United States

Olympian Clinical Research

Tampa, Florida, United States

Idaho Research

Eagle, Idaho, United States

Midwest Allergy Sinus Asthma SC

Normal, Illinois, United States

John Hopkins University

Baltimore, Maryland, United States

Institute for Asthma and Allergy PC

Chevy Chase, Maryland, United States

Chesapeake Clinical Research

White Marsh, Maryland, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Midwest Clinical Research LcLC

St Louis, Missouri, United States

Montana Medical Research

Missoula, Montana, United States

The Asthma and Allergy Center PC

Papillion, Nebraska, United States

Icahn School Of Med At Mount Sinai

New York, New York, United States

Toledo Institute of Clinical Research

Toledo, Ohio, United States

Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, United States

PCR DBA Columbia Asthma and Allergy

Clackamas, Oregon, United States

Allergy and Asthma Specialists PC

Blue Bell, Pennsylvania, United States

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, United States

National Allergy and Asthma Research LLS

North Charleston, South Carolina, United States

Bellaire Dermatology Associates

Bellaire, Texas, United States

Western Sky Medical Research

El Paso, Texas, United States

North Texas Inst For Clinical Tri

Fort Worth, Texas, United States

Allergy and Asthma Research Center PA

San Antonio, Texas, United States

Quality Assurance Research Center

San Antonio, Texas, United States

Allergy and Asthma Care of Waco

Waco, Texas, United States

Allergy Associates of Utah

Sandy City, Utah, United States

Bellingham Asthma Allergy and Immunology

Bellingham, Washington, United States

Novartis Investigative Site

CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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Mendoza, Mendoza Province, Argentina

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Santa Fe, Rosario, Argentina

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Rosario, Santa Fe Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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CABA, , Argentina

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Salta, , Argentina

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Adelaide, South Australia, Australia

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East Melbourne, Victoria, Australia

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Parkville, Victoria, Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Loverval, , Belgium

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Salvador, Estado de Bahia, Brazil

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Rio de Janeiro, Rio de Janeiro, Brazil

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Alphaville Barueri, São Paulo, Brazil

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São José do Rio Preto, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Vitacura, Santiago Metropolitan, Chile

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Osorno, , Chile

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Santiago, , Chile

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Tallinn, , Estonia

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Tartu, , Estonia

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Helsinki, , Finland

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Grenoble, , France

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Nice, , France

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Bad Bentheim, , Germany

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Frankfurt, , Germany

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Gera, , Germany

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Rotterdam, South Holland, Netherlands

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Amersfroort, , Netherlands

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Utrecht, , Netherlands

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Lipa City, Batangas, Philippines

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City of Taguig, National Capital Region, Philippines

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Makati City, , Philippines

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Pasig, , Philippines

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Quezon, , Philippines

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Bydgoszcz, , Poland

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Bucharest, District 2, Romania

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Craiova, , Romania

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Iași, , Romania

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Chelyabinsk, , Russia

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Kazan', , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Stavropol, , Russia

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Kežmarok, , Slovakia

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Komárno, , Slovakia

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Levice, , Slovakia

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Nové Zámky, , Slovakia

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Považská Bystrica, , Slovakia

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Svidník, , Slovakia

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Topoľčany, , Slovakia

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Žilina, , Slovakia

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Córdoba, Andalusia, Spain

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Granada, Andalusia, Spain

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Barcelona, Catalonia, Spain

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Alcorcón, Madrid, Spain

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Pozuelo de Alarcón, Madrid, Spain

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Pamplona, Navarre, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Valencia, , Spain

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Tunis, Tunisie, Tunisia

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Sfax, Tunusia, Tunisia

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Sousse, , Tunisia

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London, , United Kingdom

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

Countries

United States; Argentina; Australia; Belgium; Brazil; Chile; Estonia; Finland; France; Germany; India; Israel; Italy; Japan; Lebanon; Mexico; Netherlands; Philippines; Poland; Romania; Russia; Slovakia; Spain; Taiwan; Tunisia; United Kingdom; Vietnam

References

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.

Reference Type: DERIVED

PMID: 38008109 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000840-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQGE031C2303

Identifier Type: -

Identifier Source: org_study_id