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.

NCT06042478 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: CLOU064A23042022-502161-19-00
• Study Type: interventional
• Target: 470
• Locations: 23 countries
• Sites: 111

Brief Summary

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.

Conditions

Chronic Spontaneous Urticaria

Keywords

CSU; urticaria; LOU064; omalizumab; remibrutinib

Outcome Measures

Primary Outcomes (1)

• Absolute change from baseline in Weekly Urticaria Activity Score (UAS7)

  The UAS7 is the sum of the Weekly Hives Severity Score (HSS7 score) and the Weekly Itch Severity Score (ISS7 score). The possible range of the weekly UAS7 score is 0 - 42 (highest activity).

  Week 12

Secondary Outcomes (4)

• Achievement of UAS7=0 (yes/no)

  Week 12

• Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score

  Week 12

• Improvement of severity of hives, assessed as absolute change from baseline in HSS7 score

  Week 12

• Occurrence of treatment-emergent adverse events and serious adverse events (SAEs)

  up to 68 weeks

Study Arms (4)

Remibrutinib

EXPERIMENTAL

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

Drug: Remibrutinib

Placebo to remibrutinib

PLACEBO COMPARATOR

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.

Drug: Placebo to remibrutinib

Placebo to omalizumab

PLACEBO COMPARATOR

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.

Drug: Placebo to omalizumab

Omalizumab

ACTIVE COMPARATOR

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

Drug: Omalizumab

Interventions

Remibrutinib DRUG

Active treatment

Remibrutinib

Placebo to remibrutinib DRUG

Placebo followed by active treatment

Placebo to remibrutinib

Placebo to omalizumab DRUG

Placebo followed by active comparator

Placebo to omalizumab

Omalizumab DRUG

Active comparator

Omalizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (111)

Novartis Investigative Site

CABA, Buenos Aires, C1414AIF, Argentina

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Rosario, Santa Fe Province, 2000, Argentina

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Bahía Blanca, B8000JRB, Argentina

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CABA, C1012AAY, Argentina

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Capital Federal, C1023AAB, Argentina

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Mendoza, 5500, Argentina

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Porto Alegre, Rio Grande do Sul, 90560-032, Brazil

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Alphaville Barueri, São Paulo, 06454-010, Brazil

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Santo André, São Paulo, 09060-870, Brazil

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Sorocaba, São Paulo, 18040-425, Brazil

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Sofia, 1421, Bulgaria

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Sofia, 1431, Bulgaria

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Varna, 9009, Bulgaria

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Edmonton, Alberta, T6G 1C3, Canada

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Hamilton, Ontario, L8L 3C3, Canada

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Hamilton, Ontario, L8S 1G5, Canada

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London, Ontario, N6H 5L5, Canada

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Niagara Falls, Ontario, L2H 1H5, Canada

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Québec, Quebec, G1V 4W2, Canada

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Verdun, Quebec, H4G 3E7, Canada

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Brno, 602 00, Czechia

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Plzen Bolevec, 32300, Czechia

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Prague, 100 34, Czechia

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Grenoble, 38043, France

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La Rochelle, 17019, France

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Nice, 06000, France

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Pierre-Bénite, 69495, France

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Rouen, 76031, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Munich, Bavaria, 81377, Germany

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Göttingen, Lower Saxony, 37075, Germany

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Stade, Lower Saxony, 21682, Germany

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Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04103, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Bad Bentheim, 48455, Germany

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Berlin, 13353, Germany

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Bochum, 44791, Germany

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Bochum, 44793, Germany

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Hamburg, 22391, Germany

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Heidelberg, 69120, Germany

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Lübeck, 23538, Germany

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Mainz, 55131, Germany

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München, 80377, Germany

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Münster, 48149, Germany

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Osnabrück, 49074, Germany

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Tübingen, 72076, Germany

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Kaposvár, 7400, Hungary

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Ahmedabad, Gujarat, 380016, India

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Bangalore, Karnataka, 560004, India

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Belagavi, Karnataka, 590010, India

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Mysore, Karnataka, 570001, India

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Nagpur, Maharashtra, 440012, India

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Nagpur, Maharashtra, 440015, India

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Nashik, Maharashtra, 422101, India

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New Delhi, National Capital Territory of Delhi, 110029, India

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Bikaner, Rajasthan, 334003, India

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Hyderabad, Telangana, 500004, India

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Dehradun, Uttarakhand, 248001, India

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Milan, MI, 20122, Italy

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Rozzano, MI, 20089, Italy

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Modena, MO, 41124, Italy

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Roma, RM, 00186, Italy

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Siena, SI, 53100, Italy

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Muar town, Johor, 84000, Malaysia

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Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Ipoh, Perak, 30450, Malaysia

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George Town, Pulau Pinang, 10450, Malaysia

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Petaling Jaya, Selangor, 46150, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Wilayah Persekutuan, 62502, Malaysia

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Guadalajara, Jalisco, 44638, Mexico

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Cuauhtémoc, Mexico City, 06100, Mexico

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Villahermosa, Tabasco, 86035, Mexico

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Mérida, Yucatán, 97070, Mexico

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Utrecht, 3584 CX, Netherlands

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Gdansk, 80-214, Poland

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Gdansk, 80-546, Poland

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Krosno, 38-400, Poland

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Poznan, 60-823, Poland

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Bardejov, 085 01, Slovakia

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Kežmarok, 060 01, Slovakia

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Svidník, 089 01, Slovakia

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Trnava, 917 02, Slovakia

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Ansan, Gyeonggi-do, 425-801, South Korea

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Busan, 49241, South Korea

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Seoul, 03722, South Korea

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Granada, Andalusia, 18014, Spain

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Barcelona, Catalonia, 08003, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Córdoba, 14004, Spain

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Las Palmas GC, 35010, Spain

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Valencia, 46015, Spain

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Valencia, 46026, Spain

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Zurich, 8091, Switzerland

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Taipei, 10002, Taiwan

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Taoyuan District, 33305, Taiwan

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Songkhla, Hat Yai, 90110, Thailand

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Khon Kaen, THA, 40002, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Sakarya, Adapazari, 54290, Turkey (Türkiye)

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Aydin, Efeler, 09100, Turkey (Türkiye)

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Istanbul, Fatih, 34093, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, Fatih, 34098, Turkey (Türkiye)

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Denizli, Kinikli, 20070, Turkey (Türkiye)

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Birmingham, B9 5SS, United Kingdom

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Hanoi, 100000, Vietnam

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Novartis Investigative Site

Ho Chi Minh City, 700000, Vietnam

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MeSH Terms

Conditions

Chronic Urticaria; Urticaria

Interventions

remibrutinib; Omalizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 18, 2023
• Study Start: November 15, 2023
• Primary Completion: September 17, 2025
• Study Completion (Estimated): July 20, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); AR (6); PL (4); HU (1); MY (7); TU (5); IT (5); NL (1); ME (4); FR (5); BU (3); CH (1); VN (2); BR (4); SL (4); TW (2); TH (5); GB (1); ES (8); IN (11); CA (7); CZ (3); DE (19)