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

NCT05030311 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLOU064A23012022-001034-11
• Study Type: interventional
• Target: 470
• Locations: 19 countries
• Sites: 112

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.

Conditions

Chronic Spontaneous Urticaria

Keywords

BTK inhibitor; Chronic spontaneous urticaria; Urticaria activity score; Hives severity score; Itch severity score; CSU

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Weekly Urticaria Score (UAS7) at Week 12 (Scenario 1 With UAS7 as Primary Efficacy Endpoint)

  The Weekly Urticaria Activity Score (UAS7) is a simple scoring system to evaluate urticaria signs and symptoms. It is based on scoring wheals (hive severity score) and itch (itch severity score) separately on a scale of 0 (no signs/symptoms) to 3 (intense signs/symptoms) over 7 days. The final score is calculated by adding together the daily scores, which can range from 0 to 6, for 7 days. This results in a maximum total score of 42 (highest urticaria severity), and a minimum possible score of 0. This endpoint is a secondary endpoint for testing strategy Scenario 2 with Weekly Itch Severity Score (ISS7) and Weekly Hives Severity Score (HSS7) as co-primary efficacy endpoints).

  Baseline, Week 12

• Change From Baseline in Weekly Itch Severity Score (ISS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)

  The severity of the itch was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (severe). A weekly score (ISS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest itch severity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint).

  Baseline, Week 12

• Change From Baseline in Weekly Hives Severity Score (HSS7) at Week 12 (Scenario 2 With ISS7 and HSS7 as Co-primary Efficacy Endpoints)

  The hives (wheals) severity score, defined by number of hives, was recorded by the participant twice daily in their electronic Diary, on a scale of 0 (none) to 3 (\> 12 hives/12 hours). A weekly score (HSS7) was derived by adding up the average daily scores of the 7 days preceding the visit. The possible range of the weekly score was therefore 0 - 21 (highest hives activity). This endpoint is a secondary endpoint for testing strategy Scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint.

  Baseline, Week 12

Secondary Outcomes (7)

• Number of Patients Who Achieved Disease Activity Control (UAS7 ≤6)

  Week 12

• Number of Patients Who Achieved Complete Absence of Hives and Itch (UAS7 = 0)

  Week 12

• Number of Patients With Early Onset of Disease Control (UAS7 ≤ 6 at Week 2)

  Week 2

• Cumulative Number of Weeks With Disease Activity Control (UAS7 <= 6) up to Week 12

  up to Week 12

• Number of Patients Who Achieved DLQI = 0 - 1

  Week 12

Study Arms (2)

LOU064 25mg b.i.d.

EXPERIMENTAL

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

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

Placebo

PLACEBO COMPARATOR

Patients initially randomized to Placebo (Up to Week 24)

Drug: Placebo; Drug: LOU064 25 mg (b.i.d) as a tablet.

Interventions

LOU064 25 mg (b.i.d) DRUG

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

Also known as: remibrutinib

LOU064 25mg b.i.d.

Placebo DRUG

Placebo

Placebo

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

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

Also known as: remibrutinib

LOU064 25mg b.i.d.; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (112)

Novartis Investigative Site

Birmingham, Alabama, 35209, United States

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Novartis Investigative Site

North Little Rock, Arkansas, 72117, United States

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Bakersfield, California, 93301, United States

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Novartis Investigative Site

Lancaster, California, 93534, United States

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Los Angeles, California, 90025, United States

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Redwood City, California, 94063, United States

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Denver, Colorado, 80230, United States

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Novartis Investigative Site

Aventura, Florida, 33180, United States

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Finlay Medical Research

Greenacres City, Florida, 33467, United States

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Novartis Investigative Site

Sarasota, Florida, 34233, United States

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Novartis Investigative Site

Tallahassee, Florida, 32308, United States

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Albany, Georgia, 31707, United States

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Woodstock, Georgia, 30188, United States

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Evansville, Indiana, 47715, United States

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Chevy Chase, Maryland, 20815, United States

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St Louis, Missouri, 63141, United States

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Lincoln, Nebraska, 68510, United States

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Athens, Ohio, 45701, United States

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Columbus, Ohio, 43235, United States

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Toledo, Ohio, 43617, United States

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Tulsa, Oklahoma, 74136, United States

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Austin, Texas, 78759, United States

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El Paso, Texas, 79924, United States

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San Antonio, Texas, 78213, United States

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Sandy City, Utah, 84093, United States

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Bellingham, Washington, 98225, United States

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CABA, Buenos Aires, C1181ACH, Argentina

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CABA, Buenos Aires, C1414AIF, 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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Santa Fe, Rosario, S2000DBS, Argentina

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Rosario, Santa Fe Province, S2000JKR, Argentina

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Bahía Blanca, B8000JRB, Argentina

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Novartis Investigative Site

Capital Federal, C1023AAB, Argentina

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Santa Fe, S3000FIL, Argentina

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Sydney, New South Wales, 2010, Australia

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East Melbourne, Victoria, 3002, Australia

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Parkville, Victoria, 3050, Australia

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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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Novartis Investigative Site

Medellín, Antioquia, 050010, Colombia

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Barranquilla, Atlántico, 080002, Colombia

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Novartis Investigative Site

Barranquilla, 080020, Colombia

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Novartis Investigative Site

Bogotá, 110221, Colombia

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Novartis Investigative Site

Brno, Czech Republic, 656 91, Czechia

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Olomouc, CZE, 779 00, Czechia

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Novartis Investigative Site

Pilsen, 305 99, Czechia

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Novartis Investigative Site

Prague, 150 06, Czechia

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Novartis Investigative Site

Antony, 92160, France

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Bordeaux, 33075, France

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Novartis Investigative Site

Nice, 06000, France

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Pierre-Bénite, 69495, France

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Reims, 51100, France

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Rouen, 76031, France

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Debrecen, Hajdú-Bihar, 4026, Hungary

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Debrecen, 4032, Hungary

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Szeged, 6720, Hungary

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Nagpur, Maharashtra, 440012, India

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Nagpur, Maharashtra, 440015, India

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Nashik, Maharashtra, 422005, India

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New Delhi, National Capital Territory of Delhi, 110 060, India

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Hyderabad, Telangana, 500004, India

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Varanasi, Uttar Pradesh, 221005, India

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Kolkata, West Bengal, 700054, India

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Belgavi, 590010, India

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Chandigarh, 160012, India

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Novartis Investigative Site

Ancona, AN, 60126, Italy

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Milan, MI, 20162, Italy

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Pisa, PI, 56124, Italy

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Torino, TO, 10128, Italy

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Novartis Investigative Site

Obihiro, Hokkaido, 080 0013, Japan

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Yokohama, Kanagawa, 220-6208, Japan

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Kamimashi-gun, Kumamoto, 861-3106, Japan

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Takatsuki, Osaka, 569-8686, Japan

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Koto, Tokyo, 136-0074, Japan

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Fukuoka, 819 0167, Japan

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Hiroshima, 734-8551, Japan

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Novartis Investigative Site

Guadalajara, Jalisco, 44130, Mexico

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Mexico City, Mexico City, 06700, Mexico

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Villahermosa, Tabasco, 86035, Mexico

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Carolina, 00985, Puerto Rico

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San Juan, 00927, Puerto Rico

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Izhevsk, 426061, Russia

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Singapore, 308205, Singapore

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Daegu, Dalseo Gu, 42602, 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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Gwangju, 61469, South Korea

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Incheon, 405 760, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seoul, 03722, South Korea

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Novartis Investigative Site

Seoul, 07061, South Korea

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Novartis Investigative Site

Seoul, 07441, South Korea

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

Alicante, Valencia, 03010, Spain

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Valencia, Valencia, 46015, Spain

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Novartis Investigative Site

Las Palmas de Gran Canaria, 35010, Spain

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Novartis Investigative Site

Madrid, 280796, Spain

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Novartis Investigative Site

Valencia, 46026, Spain

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Novartis Investigative Site

Taipei, 10002, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Aydin, 09100, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34662, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35380, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35620, Turkey (Türkiye)

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Novartis Investigative Site

Kayseri, 38070, Turkey (Türkiye)

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Novartis Investigative Site

Sakarya, 54290, Turkey (Türkiye)

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Novartis Investigative Site

Samsun, 55139, Turkey (Türkiye)

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Novartis Investigative Site

Talas Kayseri, 38039, Turkey (Türkiye)

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Related Publications (1)

• 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.

  PMID: 40043237 DERIVED

Related Links

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

MeSH Terms

Conditions

Chronic Urticaria

Interventions

remibrutinib

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: September 1, 2021
• Study Start: November 30, 2021
• Primary Completion: December 27, 2023
• Study Completion: January 19, 2024
• Last Updated: April 8, 2025
• Results First Posted: December 2, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

TW (2); CO (4); CZ (4); JP (7); PR (2); KR (9); ES (7); FR (6); AR (9); HU (3); TU (9); AU (3); IN (9); SG (1); IT (4); ME (3); US (26); RU (1); BU (3)