Phase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo, With Omalizumab as Active Control, in Adult CSU Patients, Followed by an Open-label 52-week Optional Extension.

NCT ID: NCT06042478

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

471 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-15

Study Completion Date

2027-07-20

Brief Summary

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The purpose of the core phase of the trial is to assess the efficacy, safety and tolerability of remibrutinib (LOU064) 25 milligrams (mg) twice a day (b.i.d.) over placebo for 24 weeks and in comparison to omalizumab 300 mg every 4 weeks (q4w) for 52 weeks in participants with chronic spontaneous urticaria (CSU) inadequately controlled by H1-antihistamines (H1-AH).

The purpose of the open-label extension phase is to assess efficacy, safety and tolerability up to two years for patients treated with remibrutinib and patients transitioned from omalizumab to remibrutinib at Week 52. In the extension phase, treatment will be with remibrutinib only (i.e., no background therapy). The extension phase will also fulfill the Novartis commitment to provide post-trial access to participants of the previous core phase.

Detailed Description

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The study consists of 4 periods, and the total study duration is up to 112 weeks. Approximately 468 adult participants with CSU are expected to be randomized in the study.

Screening period: A screening period of up to 4 weeks will allow for the assessment of eligibility, determination of baseline disease activity and wash-out of prohibited medications.

Core Phase Treatment Period (52 weeks):

The treatment period will be double-dummy and double-blind, with placebo injections matching omalizumab 300 mg s.c. given to participants in the remibrutinib arm and placebo tablets matching remibrutinib 25 mg given to participants in the omalizumab arm (double-dummy). At the randomization visit, eligible participants will be randomized to one of four treatment arms.

Extension Phase Treatment Period (52 weeks): Optional open-label extension where patients receive treatment with open-label remibrutinib 25 mg, for 52 weeks.

Follow-up period:

For patients that do not enter the extension phase, there will be a 16-week, treatment-free, safety follow-up period.

Patients that enter extension phase will have a 4-week treatment-free safety follow-up period at the end of the extension phase.

All participants will be on a stable, local label-approved standard dose of a second-generation H1-AH ("background therapy") throughout the entire core phase (starting a minimum of 7 days prior to randomization until the end of the core phase).

In addition, to treat unbearable symptoms of CSU flare-ups, participants will be allowed to use a different second-generation H1-AH on an as-needed basis ("rescue therapy").

Conditions

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Chronic Spontaneous Urticaria

Keywords

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CSU urticaria LOU064 omalizumab remibrutinib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Eligible participants will be randomized to 1 of 4 treatment arms in a 2:1:1:2 ratio:

* Remibrutinib 25 mg b.i.d. arm: participants receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks
* Placebo to remibrutinib arm: participants receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.
* Placebo to omalizumab arm: participants receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.
* Omalizumab 300 mg every 4 weeks arm: participants receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.

All of the above arms are followed by an optional 52-week extension period where participants receive treatment with remibrutinib 25 mg b.i.d. for 52 weeks.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Remibrutinib

Participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 52 weeks.

Group Type EXPERIMENTAL

Remibrutinib

Intervention Type DRUG

Active treatment

Placebo to remibrutinib

Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w.

Group Type PLACEBO_COMPARATOR

Placebo to remibrutinib

Intervention Type DRUG

Placebo followed by active treatment

Placebo to omalizumab

Participants will receive placebo for remibrutinib 25 mg b.i.d. and placebo for omalizumab q4w for 24 weeks. From Week 24 to Week 52 participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d.

Group Type PLACEBO_COMPARATOR

Placebo to omalizumab

Intervention Type DRUG

Placebo followed by active comparator

Omalizumab

participants will receive omalizumab 300 mg q4w and placebo for remibrutinib b.i.d. for 52 weeks.

Group Type ACTIVE_COMPARATOR

Omalizumab

Intervention Type DRUG

Active comparator

Interventions

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Remibrutinib

Active treatment

Intervention Type DRUG

Placebo to remibrutinib

Placebo followed by active treatment

Intervention Type DRUG

Placebo to omalizumab

Placebo followed by active comparator

Intervention Type DRUG

Omalizumab

Active comparator

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male and female adult participants ≥18 years of age at the time of signing the informed consent.
* CSU duration for ≥ 6 months prior to screening.
* Diagnosis of CSU inadequately controlled by second generation H1-AH 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-AH 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.
* 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

* Prior exposure to ligelizumab, omalizumab and other biologics with any effect in CSU, including anti-IgE therapies.
* Significant bleeding risk or coagulation disorders.
* History of gastrointestinal bleeding.
* Requirement for anti-platelet or anti-coagulant medication.
* History or current hepatic disease.
* Evidence of clinically significant cardiovascular, 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.
* Evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines.
* Documented history of anaphylaxis.
* Pregnant or nursing (lactating) women.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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Rosario, Santa Fe Province, Argentina

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Bahía Blanca, , Argentina

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CABA, , Argentina

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Capital Federal, , Argentina

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Mendoza, , Argentina

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Porto Alegre, Rio Grande do Sul, Brazil

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Alphaville Barueri, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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Sorocaba, São Paulo, Brazil

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Edmonton, Alberta, Canada

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Hamilton, Ontario, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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Niagara Falls, Ontario, Canada

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Québec, Quebec, Canada

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Verdun, Quebec, Canada

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Brno, , Czechia

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Plzen Bolevec, , Czechia

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Prague, , Czechia

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Grenoble, , France

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La Rochelle, , France

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Nice, , France

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Pierre-Bénite, , France

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Rouen, , France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Munich, Bavaria, Germany

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Göttingen, Lower Saxony, Germany

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Dresden, Saxony, Germany

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Leipzig, Saxony, Germany

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Halle, Saxony-Anhalt, Germany

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Bad Bentheim, , Germany

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Berlin, , Germany

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Bochum, , Germany

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Bochum, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Lübeck, , Germany

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Mainz, , Germany

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München, , Germany

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Münster, , Germany

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Osnabrück, , Germany

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Stade, , Germany

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Tübingen, , Germany

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Kaposvár, , Hungary

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Ahmedabad, Gujarat, India

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Bangalore, Karnataka, India

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Belagavi, Karnataka, India

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Mysore, Karnataka, India

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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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Bikaner, Rajasthan, India

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Hyderabad, Telangana, India

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Dehradun, Uttarakhand, India

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Milan, MI, Italy

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Rozzano, MI, Italy

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Modena, MO, Italy

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Roma, RM, Italy

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Siena, SI, Italy

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Muar town, Johor, Malaysia

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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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Petaling Jaya, Selangor, Malaysia

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Kuala Lumpur, , Malaysia

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Wilayah Persekutuan, , Malaysia

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Guadalajara, Jalisco, Mexico

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Cuauhtémoc, Mexico City, Mexico

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Villahermosa, Tabasco, Mexico

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Mérida, Yucatán, Mexico

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Utrecht, , Netherlands

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Gdansk, , Poland

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Gdansk, , Poland

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Krosno, , Poland

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Poznan, , Poland

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Bardejov, , Slovakia

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Kežmarok, , Slovakia

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Svidník, , Slovakia

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Trnava, , Slovakia

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Ansan, Gyeonggi-do, South Korea

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Busan, , South Korea

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Seoul, , South Korea

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Granada, Andalusia, Spain

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Barcelona, Catalonia, Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Las Palmas GC, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zurich, , Switzerland

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Songkhla, Hat Yai, Thailand

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Khon Kaen, THA, Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

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Chiang Mai, , Thailand

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Sakarya, Adapazari, Turkey (Türkiye)

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Aydin, Efeler, Turkey (Türkiye)

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Istanbul, Fatih, Turkey (Türkiye)

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Istanbul, Fatih, Turkey (Türkiye)

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Denizli, Kinikli, Turkey (Türkiye)

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Birmingham, , United Kingdom

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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Australia Argentina Brazil Bulgaria Canada Czechia France Germany Hungary India Italy Malaysia Mexico Netherlands Poland Slovakia South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

Other Identifiers

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2022-502161-19-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CLOU064A2304

Identifier Type: -

Identifier Source: org_study_id