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

NCT ID: NCT03580369

Last Updated: 2023-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1072 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-17
• Study Completion Date: 2022-06-14

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.

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 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

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

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

Locations

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Gilbert, Arizona, United States

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Litchfield Park, Arizona, United States

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Scottsdale, Arizona, United States

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Little Rock, Arkansas, United States

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Bakersfield, California, United States

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Huntington Beach, California, United States

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Long Beach, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Greenacres City, Florida, United States

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Tallahassee, Florida, United States

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Tampa, Florida, United States

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Boise, Idaho, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Overland Park, Kansas, United States

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Bangor, Maine, United States

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Waldorf, Maryland, United States

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Clarkston, Michigan, United States

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Ypsilanti, Michigan, United States

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Plymouth, Minnesota, United States

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Asheville, North Carolina, United States

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Cincinnati, Ohio, United States

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Tulsa, Oklahoma, United States

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Medford, Oregon, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Pflugerville, Texas, United States

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San Antonio, Texas, United States

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South Burlington, Vermont, United States

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CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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Ciudad Autonoma de Bs As, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Buenos Aires, Nueve De Julio, Argentina

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Bahía Blanca, , Argentina

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Buenos Aires, , Argentina

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Capital Federal, , Argentina

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Innsbruck, , Austria

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Vienna, , Austria

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Vitória, Espírito Santo, Brazil

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Alphaville Barueri, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Pleven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Hamilton, Ontario, Canada

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Kingston, Ontario, Canada

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Mississauga, Ontario, Canada

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Toronto, Ontario, Canada

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Waterloo, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Medellín, Antioquia, Colombia

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Bogotá, , Colombia

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Zagreb, , Croatia

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Teplice, CZE, Czechia

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Prague, Prague 1, Czechia

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Olomouc, , Czechia

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Pilsen, , Czechia

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Copenhagen NV, , Denmark

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Herlev, , Denmark

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Bordeaux, , France

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Montpellier, , France

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Marburg, , Germany

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Memmingen, , Germany

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Athens, GR, Greece

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Guatemala City, , Guatemala

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Szeged, Csongrád megye, Hungary

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Navi Mumbai, Maharashtra, India

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New Delhi, , India

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Kuala Lumpur, Kuala Lumpur, Malaysia

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Ipoh, Perak, Malaysia

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George Town, Pulau Pinang, Malaysia

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Muscat, , Oman

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Miraflores, Lima region, Peru

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San Borja, Lima region, Peru

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Ksawerów, POL, Poland

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Kielce, , Poland

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Smolensk, , Russia

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Cape Town, Western Province, South Africa

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Durban, , South Africa

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Daegu, Dalseo Gu, South Korea

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Bundang Gu, Gyeonggi-do, South Korea

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Hwaseong-si, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Seoul, Korea, South Korea

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Seoul, Seocho Gu, South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Málaga, Andalusia, Spain

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Seville, Andalusia, Spain

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L'Hospitalet de Llobregat, Barcelona, Spain

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Bilbao, Basque Country, Spain

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Barcelona, Catalonia, Spain

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Alicante, Valencia, Spain

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Barcelona, , Spain

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Malmo, , Sweden

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Bangkoknoi, Bangkok, Thailand

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Bangkok, Phayathai, Thailand

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Aydin, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Okmeydanı, , Turkey (Türkiye)

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Samsun, , Turkey (Türkiye)

Countries

United States; Argentina; Austria; Brazil; Bulgaria; Canada; Colombia; Croatia; Czechia; Denmark; France; Germany; Greece; Guatemala; Hungary; India; Malaysia; Oman; Peru; Poland; Puerto Rico; Russia; Singapore; South Africa; South Korea; Spain; Sweden; Thailand; Turkey (Türkiye)

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

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1511

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

Other Identifiers

2018-000839-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CQGE031C2302

Identifier Type: -

Identifier Source: org_study_id