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

NCT ID: NCT05032157

Last Updated: 2025-04-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

455 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2024-01-05

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 design of this study was a replicate of another Phase III study, CLOU046A2301 (NCT05030311).

The study population consisted of female and male adult patients with CSU inadequately controlled by second generation H1-AHs at least at a locally label approved dose. All patients were on a stable, locally label approved dose of a second generation H1 AH (background therapy) throughout the entire study (starting a minimum of 7 days prior to randomization until the end of the study). To treat unbearable symptoms of CSU, patients were allowed to use another second generation H1-AH on an as-needed basis (rescue therapy). Eligible patients were randomly assigned to the treatment arms in a 2:1 ratio to remibrutinib or placebo arm (300 in the remibrutinib arm and 150 in placebo arm) and stratified based on prior exposure to anti-IgE biologics for CSU and geographic region.

An extension Phase IIIb study, CLOU064A2303B (NCT05513001), was initiated to allow CLOU064A2302 eligible patients to roll over after completion of the open-label treatment period.

There were two distinct testing strategies (scenario 1 with Weekly Urticaria Activity Score (UAS7) as the primary efficacy endpoint and scenario 2 with Weekly Itch Severity Score (ISS7) and Weekly Hives Severity Score (HSS7) as the co-primary efficacy endpoints) based on two primary objective scenarios related to regional regulatory precedent and Health Authorities' feedback.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Spontaneous Urticaria

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

LOU064 25mg b.i.d.

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)

Group Type EXPERIMENTAL

LOU064 (blinded)

Intervention Type DRUG

LOU064 (blinded) active treatment

LOU064 (open-label)

Intervention Type DRUG

LOU064 (open-label) active treatment

Placebo

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)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

LOU064 (open-label)

Intervention Type DRUG

LOU064 (open-label) active treatment

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

LOU064 (blinded)

LOU064 (blinded) active treatment

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

LOU064 (open-label)

LOU064 (open-label) active treatment

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

remibrutinib remibrutinib

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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).

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Cahaba Derm and skin hlth ctr 27

Birmingham, Alabama, United States

Site Status

Research Solutions of Arizona

Litchfield Park, Arizona, United States

Site Status

Little Rock Allergy and Asthma Clnc

Little Rock, Arkansas, United States

Site Status

Allergy and Asthma Medical Group and Research Center

San Diego, California, United States

Site Status

UCONN Health Dermatology

Farmington, Connecticut, United States

Site Status

Miami Dade Medical Research

Miami, Florida, United States

Site Status

Ziaderm Research LLC

North Miami Beach, Florida, United States

Site Status

Riverchase Dermatology

Pembroke Pines, Florida, United States

Site Status

TrueBlue Clinical Research

Tampa, Florida, United States

Site Status

AeroAllergy Research Laboratories of Savannah Inc

Savannah, Georgia, United States

Site Status

Treasure Valley Medical Research

Boise, Idaho, United States

Site Status

Northshore University Health System

Glenview, Illinois, United States

Site Status

Asthma and Allergy Center of Chicago S C

River Forest, Illinois, United States

Site Status

The Indiana Clinical Trials Center

Plainfield, Indiana, United States

Site Status

Allergy and Asthma Specialist P S C

Owensboro, Kentucky, United States

Site Status

John Hopkins University

Baltimore, Maryland, United States

Site Status

Chesapeake Clinical Research

White Marsh, Maryland, United States

Site Status

Revival Research Institute

Troy, Michigan, United States

Site Status

Montana Medical Research

Missoula, Montana, United States

Site Status

Allergy Asthma Assoc Monmouth

Little Silver, New Jersey, United States

Site Status

Peters Medical Research

High Point, North Carolina, United States

Site Status

CR Services Acquisition US

Dublin, Ohio, United States

Site Status

Ohio Clinical Research Associates

Mayfield Heights, Ohio, United States

Site Status

Allergy Asthma and Clinical Research

Oklahoma City, Oklahoma, United States

Site Status

Allergy and Clinical Immunology Associates

Pittsburgh, Pennsylvania, United States

Site Status

National Allergy and Asthma Research LLS

North Charleston, South Carolina, United States

Site Status

STAAMP Research LLC

San Antonio, Texas, United States

Site Status

Intermountain Clinical Research

Salt Lake City, Utah, United States

Site Status

Seattle Allergy and Asthma Rsch

Seattle, Washington, United States

Site Status

Allergy Asthma and amp Sinus Ctr S C

Greenfield, Wisconsin, United States

Site Status

Novartis Investigative Site

Linz, Upper Austria, Austria

Site Status

Novartis Investigative Site

São Bernardo do Campo, São Paulo, Brazil

Site Status

Novartis Investigative Site

Edmonton, Alberta, Canada

Site Status

Novartis Investigative Site

Fredericton, New Brunswick, Canada

Site Status

Novartis Investigative Site

Kingston, Ontario, Canada

Site Status

Novartis Investigative Site

London, Ontario, Canada

Site Status

Novartis Investigative Site

Niagara Falls, Ontario, Canada

Site Status

Novartis Investigative Site

Ottawa, Ontario, Canada

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Verdun, Quebec, Canada

Site Status

Novartis Investigative Site

Guangzhou, Guangdong, China

Site Status

Novartis Investigative Site

Guangzhou, Guangdong, China

Site Status

Novartis Investigative Site

Guangdong, Guangzhou, China

Site Status

Novartis Investigative Site

Wuhan, Hubei, China

Site Status

Novartis Investigative Site

Wuxi, Jiangsu, China

Site Status

Novartis Investigative Site

Changchun, Jilin, China

Site Status

Novartis Investigative Site

Shenyang, Liaoning, China

Site Status

Novartis Investigative Site

Chengdu, Sichuan, China

Site Status

Novartis Investigative Site

Hangzhou, Zhejiang, China

Site Status

Novartis Investigative Site

Hangzhou, Zhejiang, China

Site Status

Novartis Investigative Site

Yiwu, Zhejiang, China

Site Status

Novartis Investigative Site

Beijing, , China

Site Status

Novartis Investigative Site

Beijing, , China

Site Status

Novartis Investigative Site

Shanghai, , China

Site Status

Novartis Investigative Site

Shanghai, , China

Site Status

Novartis Investigative Site

Tianjin, , China

Site Status

Novartis Investigative Site

Copenhagen NV, , Denmark

Site Status

Novartis Investigative Site

Hellerup, , Denmark

Site Status

Novartis Investigative Site

Bad Bentheim, , Germany

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Berlin, , Germany

Site Status

Novartis Investigative Site

Bramsche, , Germany

Site Status

Novartis Investigative Site

Dresden, , Germany

Site Status

Novartis Investigative Site

Göttingen, , Germany

Site Status

Novartis Investigative Site

Halle, , Germany

Site Status

Novartis Investigative Site

Halle S, , Germany

Site Status

Novartis Investigative Site

Hamburg, , Germany

Site Status

Novartis Investigative Site

Langenau, , Germany

Site Status

Novartis Investigative Site

Leipzig, , Germany

Site Status

Novartis Investigative Site

Lübeck, , Germany

Site Status

Novartis Investigative Site

Mainz, , Germany

Site Status

Novartis Investigative Site

Marburg, , Germany

Site Status

Novartis Investigative Site

Merzig, , Germany

Site Status

Novartis Investigative Site

München, , Germany

Site Status

Novartis Investigative Site

München, , Germany

Site Status

Novartis Investigative Site

Tübingen, , Germany

Site Status

Novartis Investigative Site

Ahmedabad, Gujarat, India

Site Status

Novartis Investigative Site

Bangalore, Karnataka, India

Site Status

Novartis Investigative Site

Mysore, Karnataka, India

Site Status

Novartis Investigative Site

Nagpur, Maharashtra, India

Site Status

Novartis Investigative Site

Nagpur, Maharashtra, India

Site Status

Novartis Investigative Site

Nashik, Maharashtra, India

Site Status

Novartis Investigative Site

Dehradun, Uttarakhand, India

Site Status

Novartis Investigative Site

Kolkata, West Bengal, India

Site Status

Novartis Investigative Site

New Delhi, , India

Site Status

Novartis Investigative Site

Surat, , India

Site Status

Novartis Investigative Site

Muar town, Johor, Malaysia

Site Status

Novartis Investigative Site

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status

Novartis Investigative Site

Ipoh, Perak, Malaysia

Site Status

Novartis Investigative Site

Pulau Pinang, , Malaysia

Site Status

Novartis Investigative Site

Wilayah Persekutuan, , Malaysia

Site Status

Novartis Investigative Site

Bialystok, , Poland

Site Status

Novartis Investigative Site

Lodz, , Poland

Site Status

Novartis Investigative Site

Poznan, , Poland

Site Status

Novartis Investigative Site

Poznan, , Poland

Site Status

Novartis Investigative Site

Warsaw, , Poland

Site Status

Novartis Investigative Site

Ryazan, , Russia

Site Status

Novartis Investigative Site

Ryazan, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Stavropol, , Russia

Site Status

Novartis Investigative Site

Kežmarok, , Slovakia

Site Status

Novartis Investigative Site

Košice, , Slovakia

Site Status

Novartis Investigative Site

Svidník, , Slovakia

Site Status

Novartis Investigative Site

Topoľčany, , Slovakia

Site Status

Novartis Investigative Site

Pretoria, Gauteng, South Africa

Site Status

Novartis Investigative Site

Cape Town, Western Province, South Africa

Site Status

Novartis Investigative Site

Cape Town, , South Africa

Site Status

Novartis Investigative Site

Bern, , Switzerland

Site Status

Novartis Investigative Site

Zurich, , Switzerland

Site Status

Novartis Investigative Site

Zurich, , Switzerland

Site Status

Novartis Investigative Site

Taichung, , Taiwan

Site Status

Novartis Investigative Site

Taoyuan District, , Taiwan

Site Status

Novartis Investigative Site

Bangkoknoi, Bangkok, Thailand

Site Status

Novartis Investigative Site

Khon Kaen, THA, Thailand

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Chiang Mai, , Thailand

Site Status

Novartis Investigative Site

Leeds, West Yorkshire, United Kingdom

Site Status

Novartis Investigative Site

Cardiff, , United Kingdom

Site Status

Novartis Investigative Site

Oxford, , United Kingdom

Site Status

Novartis Investigative Site

Hanoi, , Vietnam

Site Status

Novartis Investigative Site

Ho Chi Minh City, , Vietnam

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Austria Brazil Canada China Denmark Germany India Malaysia Poland Russia Slovakia South Africa Switzerland Taiwan Thailand United Kingdom Vietnam

References

Explore related publications, articles, or registry entries linked to this study.

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

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

Access external resources that provide additional context or updates about the study.

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2430

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

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2021-000424-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLOU064A2302

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.