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

NCT05032157 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CLOU064A23022021-000424-35
• Study Type: interventional
• Target: 455
• Locations: 18 countries
• Sites: 122

Brief Summary

The purpose of this study was to establish the efficacy, safety, and tolerability of Remibrutinib 25 mg b.i.d. in adult patients suffering from chronic spontaneous urticaria (CSU) inadequately controlled by second generation H1-antihistamines (H1-AHs) in comparison to placebo.

Conditions

Chronic Spontaneous Urticaria

Keywords

Bruton Tyrosine Kinase (BTK) inhibitor; Chronic Spontaneous Urticaria (CSU); Urticaria Activity Score (UAS); Weekly Urticaria Activity Score (UAS7); Hives Severity Score (HSS); Weekly Hives Severity Score (HSS7); Itch Severity Score (ISS); Weekly Itch Severity Score (ISS7); Angioedema Activity Score (AAS); Weekly Angioedema Activity Score (AAS7); Dermatology Life Quality Index (DLQI)

Outcome Measures

Primary Outcomes (3)

• Mean Change From Baseline in Weekly Urticaria Activity 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

• Mean 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

• Mean 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 Participants Who Achieved Disease Activity Control (UAS7 =< 6) at Week 12

  Week 12

• Number of Participants Who Achieved Complete Absence of Hives and Itch (UAS7 = 0) at Week 12

  Week 12

• Number of Participants Who Achieved Early Onset of Disease Activity Control (UAS7 =< 6) at Week 2

  Week 2

• Number of Participants Who Achieved Dermatology Life Quality Index (DLQI) = 0-1 at Week 12

  Week 12

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

  Up to Week 12

Study Arms (2)

LOU064 25mg b.i.d.

EXPERIMENTAL

LOU064A (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open- label) taken orally b.i.d. for 28 weeks. Randomised in 2:1 ratio (active vs placebo)

Drug: LOU064 (blinded); Drug: LOU064 (open-label)

Placebo

PLACEBO COMPARATOR

LOU064A placebo (blinded) taken orally for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for 28 weeks. Randomised in 2:1 ratio (active vs placebo)

Drug: Placebo; Drug: LOU064 (open-label)

Interventions

LOU064 (blinded) DRUG

LOU064 (blinded) active treatment

Also known as: remibrutinib

LOU064 25mg b.i.d.

Placebo DRUG

Placebo

Placebo

LOU064 (open-label) DRUG

LOU064 (open-label) active treatment

Also known as: remibrutinib

LOU064 25mg b.i.d.; Placebo

Eligibility Criteria

• Age: 18 Years - 100 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 at the time of screening.
• 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 (CU) (chronic inducible urticaria (CINDU)) 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 (122)

Cahaba Derm and skin hlth ctr 27

Birmingham, Alabama, 35244, United States

Location

Research Solutions of Arizona

Litchfield Park, Arizona, 85340, United States

Location

Little Rock Allergy and Asthma Clnc

Little Rock, Arkansas, 72205, United States

Location

Allergy and Asthma Medical Group and Research Center

San Diego, California, 92123, United States

Location

UCONN Health Dermatology

Farmington, Connecticut, 06030-2840, United States

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Miami Dade Medical Research

Miami, Florida, 33176, United States

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Ziaderm Research LLC

North Miami Beach, Florida, 33162, United States

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Riverchase Dermatology

Pembroke Pines, Florida, 33028, United States

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TrueBlue Clinical Research

Tampa, Florida, 33609, United States

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AeroAllergy Research Laboratories of Savannah Inc

Savannah, Georgia, 31406, United States

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Treasure Valley Medical Research

Boise, Idaho, 83706, United States

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Northshore University Health System

Glenview, Illinois, 60077, United States

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Asthma and Allergy Center of Chicago S C

River Forest, Illinois, 60305, United States

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The Indiana Clinical Trials Center

Plainfield, Indiana, 46168, United States

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Allergy and Asthma Specialist P S C

Owensboro, Kentucky, 42301, United States

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John Hopkins University

Baltimore, Maryland, 21204, United States

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Chesapeake Clinical Research

White Marsh, Maryland, 21162, United States

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Revival Research Institute

Troy, Michigan, 48084, United States

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Montana Medical Research

Missoula, Montana, 59808, United States

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Allergy Asthma Assoc Monmouth

Little Silver, New Jersey, 07739, United States

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Peters Medical Research

High Point, North Carolina, 27260, United States

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CR Services Acquisition US

Dublin, Ohio, 43016, United States

Location

Ohio Clinical Research Associates

Mayfield Heights, Ohio, 44124, United States

Location

Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, 73120, United States

Location

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, 15241, United States

Location

National Allergy and Asthma Research LLS

North Charleston, South Carolina, 29420, United States

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STAAMP Research LLC

San Antonio, Texas, 78229, United States

Location

Intermountain Clinical Research

Salt Lake City, Utah, 84102, United States

Location

Seattle Allergy and Asthma Rsch

Seattle, Washington, 98115, United States

Location

Allergy Asthma and amp Sinus Ctr S C

Greenfield, Wisconsin, 53228, United States

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Novartis Investigative Site

Linz, Upper Austria, A 4020, Austria

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Novartis Investigative Site

São Bernardo do Campo, São Paulo, 09715 090, Brazil

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Novartis Investigative Site

Edmonton, Alberta, T6G 1C3, Canada

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Novartis Investigative Site

Fredericton, New Brunswick, E3B 1G9, Canada

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Novartis Investigative Site

Kingston, Ontario, K7L 2V7, Canada

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Novartis Investigative Site

London, Ontario, N6H 5L5, Canada

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Novartis Investigative Site

Niagara Falls, Ontario, L2H 1H5, Canada

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Novartis Investigative Site

Ottawa, Ontario, K1G 6C6, Canada

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Novartis Investigative Site

Toronto, Ontario, M3B 3S6, Canada

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Novartis Investigative Site

Verdun, Quebec, H4G 3E7, Canada

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Novartis Investigative Site

Guangzhou, Guangdong, 510515, China

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Novartis Investigative Site

Guangzhou, Guangdong, 510630, China

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Novartis Investigative Site

Guangdong, Guangzhou, 510091, China

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Wuhan, Hubei, 430022, China

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Novartis Investigative Site

Wuxi, Jiangsu, 214002, China

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Changchun, Jilin, 130021, China

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Shenyang, Liaoning, 110011, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310003, China

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Novartis Investigative Site

Hangzhou, Zhejiang, 310016, China

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Novartis Investigative Site

Yiwu, Zhejiang, 322000, China

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Novartis Investigative Site

Beijing, 100050, China

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Novartis Investigative Site

Beijing, 100191, China

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Shanghai, 200040, China

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Novartis Investigative Site

Shanghai, 200443, China

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Novartis Investigative Site

Tianjin, 300052, China

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Novartis Investigative Site

Copenhagen NV, 2400, Denmark

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Novartis Investigative Site

Hellerup, 2900, Denmark

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Novartis Investigative Site

Bad Bentheim, 48455, Germany

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Novartis Investigative Site

Berlin, 13187, Germany

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Berlin, 13353, Germany

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Bramsche, 49565, Germany

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Dresden, 01307, Germany

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Göttingen, 37075, Germany

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Novartis Investigative Site

Halle, 06108, Germany

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Novartis Investigative Site

Halle S, 06120, Germany

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Novartis Investigative Site

Hamburg, 22391, Germany

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Langenau, 89129, Germany

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Leipzig, 04103, Germany

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Lübeck, 23538, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Novartis Investigative Site

Marburg, 35039, Germany

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Novartis Investigative Site

Merzig, 66663, Germany

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Novartis Investigative Site

München, 80377, Germany

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Novartis Investigative Site

München, 81377, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ahmedabad, Gujarat, 380016, India

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Novartis Investigative Site

Bangalore, Karnataka, 571401, India

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Novartis Investigative Site

Mysore, Karnataka, 570001, India

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Novartis Investigative Site

Nagpur, Maharashtra, 440001, India

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Novartis Investigative Site

Nagpur, Maharashtra, 440008, India

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Novartis Investigative Site

Nashik, Maharashtra, 422101, India

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Novartis Investigative Site

Dehradun, Uttarakhand, 248001, India

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Novartis Investigative Site

Kolkata, West Bengal, 700073, India

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Novartis Investigative Site

New Delhi, 110029, India

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Novartis Investigative Site

Surat, 395001, India

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Novartis Investigative Site

Muar town, Johor, 84000, Malaysia

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Novartis Investigative Site

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Novartis Investigative Site

Ipoh, Perak, 30450, Malaysia

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Novartis Investigative Site

Pulau Pinang, 10990, Malaysia

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Novartis Investigative Site

Wilayah Persekutuan, 62502, Malaysia

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Novartis Investigative Site

Bialystok, 15 276, Poland

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Novartis Investigative Site

Lodz, 90-265, Poland

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Novartis Investigative Site

Poznan, 60-693, Poland

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Novartis Investigative Site

Poznan, 60-823, Poland

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Novartis Investigative Site

Warsaw, 02-507, Poland

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Novartis Investigative Site

Ryazan, 390039, Russia

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Novartis Investigative Site

Ryazan, 390046, Russia

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Novartis Investigative Site

Saint Petersburg, 196158, Russia

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Novartis Investigative Site

Saint Petersburg, 199226, Russia

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Novartis Investigative Site

Stavropol, 355000, Russia

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Novartis Investigative Site

Kežmarok, 060 01, Slovakia

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Novartis Investigative Site

Košice, 041 90, Slovakia

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Novartis Investigative Site

Svidník, 08901, Slovakia

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Novartis Investigative Site

Topoľčany, 95501, Slovakia

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Novartis Investigative Site

Pretoria, Gauteng, 0009, South Africa

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Novartis Investigative Site

Cape Town, Western Province, 7700, South Africa

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Novartis Investigative Site

Cape Town, 7700, South Africa

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Novartis Investigative Site

Bern, 3010, Switzerland

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Novartis Investigative Site

Zurich, 8006, Switzerland

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Novartis Investigative Site

Zurich, 8091, Switzerland

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Novartis Investigative Site

Taichung, 407219, Taiwan

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Novartis Investigative Site

Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Bangkoknoi, Bangkok, 10700, Thailand

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Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Leeds, West Yorkshire, LS9 7TF, United Kingdom

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Novartis Investigative Site

Cardiff, CF14 4XW, United Kingdom

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Novartis Investigative Site

Oxford, OX3 7LE, United Kingdom

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Novartis Investigative Site

Hanoi, 100000, Vietnam

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Novartis Investigative Site

Ho Chi Minh City, 7000, Vietnam

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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 2, 2021
• Study Start: December 1, 2021
• Primary Completion: December 18, 2023
• Study Completion: January 5, 2024
• Last Updated: April 8, 2025
• Results First Posted: November 1, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); RU (5); TH (4); AU (1); CA (8); TW (2); CN (16); DE (18); VN (2); CH (3); US (30); ZA (3); DK (2); SL (4); MY (5); IN (10); BR (1); PL (5)