A Phase 3 Study of Efficacy and Safety of Remibrutinib in the Treatment of CSU in Adults Inadequately Controlled by H1 Antihistamines

NCT ID: NCT05030311

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 470 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-30
• Study Completion Date: 2024-01-19

Brief Summary

The purpose of this study was to establish the efficacy, safety, and tolerability of remibrutinib (LOU064) in adult participants suffering from chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines in comparison to placebo.

Detailed Description

This was a global Phase III multi-centered, randomized,double-blind, parallel-group, placebo-controlled study investigating the safety, tolerability, and efficacy of remibrutinib (25 mg b.i.d.) in adult patients with CSU inadequately controlled by second generation H1-antihistamines (H1-AHs). The study consisted of four periods, the total study duration was up to 60 weeks: Screening period of up to 4 weeks, Double-blind placebo-controlled treatment period of 24 weeks, Open-label treatment period with remibrutinib period of 28 weeks, and treatment-free follow-up period of 4 weeks. The planned sample size was approximately 450 patients randomized in 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm).

Conditions

Chronic Spontaneous Urticaria

Study Design

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

Study Groups

LOU064 25mg b.i.d.

Patients initially randomized to Remibrutinib during the Double-blind treatment period and continued Remibrutinib during the Open-label treatment period (Up to Week 52)

Group Type: EXPERIMENTAL

LOU064 25 mg (b.i.d)

Intervention Type: DRUG

LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet.

LOU064 25 mg (b.i.d) as a tablet.

Intervention Type: DRUG

LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet in open label phase.

Placebo

Patients initially randomized to Placebo (Up to Week 24)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

LOU064 25 mg (b.i.d) as a tablet.

Intervention Type: DRUG

LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet in open label phase.

Interventions

LOU064 25 mg (b.i.d)

LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

LOU064 25 mg (b.i.d) as a tablet.

LOU064 25 mg was administered by oral route twice a day (b.i.d) as a tablet in open label phase.

Intervention Type: DRUG

Other Intervention Names

remibrutinib; remibrutinib

Eligibility Criteria

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study.
• Male and female adult participants ≥18 years of age.
• CSU duration for ≥ 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation).
• Diagnosis of CSU inadequately controlled by second generation H1 antihistamines at the time of randomization defined as:
• The presence of itch and hives for ≥6 consecutive weeks prior to screening despite the use of second generation H1-antihistamines during this time period
• UAS7 score (range 0-42) ≥16, ISS7 score (range 0-21) ≥ 6 and HSS7 score (range 0-21) ≥ 6 during the 7 days prior to randomization (Day 1)
• Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants medical history).
• Willing and able to complete an Urticaria Patient Daily Diary (UPDD) for the duration of the study and adhere to the study protocol.
• Participants must not have had more than one missing UPDD entry (either morning or evening) in the 7 days prior to randomization (Day 1).

Exclusion Criteria

• Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
• Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary urticaria, or drug-induced urticaria
• Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
• Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York heart association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to Visit 1), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
• Significant bleeding risk or coagulation disorders
• History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. requiring hospitalization or blood transfusion)
• Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is prohibited.
• Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOAC))
• History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening

• Minimum Eligible Age: 18 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

Novartis Investigative Site

Birmingham, Alabama, United States

Novartis Investigative Site

North Little Rock, Arkansas, United States

Novartis Investigative Site

Bakersfield, California, United States

Novartis Investigative Site

Lancaster, California, United States

Novartis Investigative Site

Los Angeles, California, United States

Novartis Investigative Site

Redwood City, California, United States

Novartis Investigative Site

Denver, Colorado, United States

Novartis Investigative Site

Aventura, Florida, United States

Finlay Medical Research

Greenacres City, Florida, United States

Novartis Investigative Site

Sarasota, Florida, United States

Novartis Investigative Site

Tallahassee, Florida, United States

Novartis Investigative Site

Albany, Georgia, United States

Novartis Investigative Site

Woodstock, Georgia, United States

Novartis Investigative Site

Evansville, Indiana, United States

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Chevy Chase, Maryland, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Athens, Ohio, United States

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Columbus, Ohio, United States

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Toledo, Ohio, United States

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Tulsa, Oklahoma, United States

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Austin, Texas, United States

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El Paso, Texas, United States

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San Antonio, Texas, United States

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Sandy City, Utah, United States

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Bellingham, Washington, United States

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CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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La Plata, Buenos Aires, Argentina

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Buenos Aires, Nueve De Julio, Argentina

Novartis Investigative Site

Santa Fe, Rosario, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

Bahía Blanca, , Argentina

Novartis Investigative Site

Capital Federal, , Argentina

Novartis Investigative Site

Santa Fe, , Argentina

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Sydney, New South Wales, Australia

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East Melbourne, Victoria, Australia

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Parkville, Victoria, Australia

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Pleven, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Medellín, Antioquia, Colombia

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Barranquilla, Atlántico, Colombia

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Brno, Czech Republic, Czechia

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Olomouc, CZE, Czechia

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Pilsen, , Czechia

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Prague, , Czechia

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Antony, , France

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Bordeaux, , France

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Nice, , France

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Pierre-Bénite, , France

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Reims, , France

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Rouen, , France

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Debrecen, Hajdú-Bihar, Hungary

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Debrecen, , Hungary

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Szeged, , Hungary

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Nagpur, Maharashtra, India

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Nagpur, Maharashtra, India

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Nashik, Maharashtra, India

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New Delhi, National Capital Territory of Delhi, India

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Hyderabad, Telangana, India

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Varanasi, Uttar Pradesh, India

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Kolkata, West Bengal, India

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Belgavi, , India

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Chandigarh, , India

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Ancona, AN, Italy

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Milan, MI, Italy

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Pisa, PI, Italy

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Torino, TO, Italy

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Obihiro, Hokkaido, Japan

Novartis Investigative Site

Yokohama, Kanagawa, Japan

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Kamimashi-gun, Kumamoto, Japan

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Takatsuki, Osaka, Japan

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Koto, Tokyo, Japan

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Fukuoka, , Japan

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Hiroshima, , Japan

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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Villahermosa, Tabasco, Mexico

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Carolina, , Puerto Rico

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San Juan, , Puerto Rico

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Izhevsk, , Russia

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Singapore, , Singapore

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Daegu, Dalseo Gu, 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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Gwangju, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Alicante, Valencia, Spain

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Valencia, Valencia, Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

Novartis Investigative Site

Valencia, , Spain

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Taipei, , Taiwan

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Taipei, , Taiwan

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Aydin, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kayseri, , Turkey (Türkiye)

Novartis Investigative Site

Sakarya, , Turkey (Türkiye)

Novartis Investigative Site

Samsun, , Turkey (Türkiye)

Novartis Investigative Site

Talas Kayseri, , Turkey (Türkiye)

Countries

United States; Argentina; Australia; Bulgaria; Colombia; Czechia; France; Hungary; India; Italy; Japan; Mexico; Puerto Rico; Russia; Singapore; South Korea; Spain; Taiwan; Turkey (Türkiye)

References

Metz M, Gimenez-Arnau A, Hide M, Lebwohl M, Mosnaim G, Saini S, Sussman G, Szalewski R, Haemmerle S, Lheritier K, Martzloff ED, Seko N, Wang P, Zharkov A, Maurer M; REMIX-1 and REMIX-2 Investigators; REMIX-1 Investigators; REMIX-2 Investigators. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025 Mar 6;392(10):984-994. doi: 10.1056/NEJMoa2408792.

Reference Type: DERIVED

PMID: 40043237 (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=2429

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

Other Identifiers

2022-001034-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLOU064A2301

Identifier Type: -

Identifier Source: org_study_id