24 Weeks Double-blind Randomized Placebo-controlled Trial to Evaluate Efficacy, PK, Safety of LOU064 in Adolescents (12 - <18) With CSU and Inadequate Response to H1-antihistamine Followed by Optional 3 Years Open-label Extension and an Optional 3 Years Safety Long-term Treatment-free Follow-up

A Double-blind, Randomized, Placebo-controlled Trial to Evaluate the Efficacy, Pharmacokinetics and Safety of Remibrutinib (LOU064) for 24 Weeks in Adolescents From 12 to Less Than 18 Years of Age With Chronic Spontaneous Urticaria Inadequately Controlled by H1-antihistamines Followed by an Optional Open-label Extension for up to Another 3 Years and an Optional Safety Long-term Treatment-free Follow-up Period for up to an Additional 3 Years

The purpose of this trial is:

1. to assess the efficacy, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to < 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines
2. to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment
3. to collect safety data in this population for up to three years after the last dose of study treatment

Study Overview

• Status: Recruiting
• Conditions: Chronic Spontaneous Urticaria
• Intervention / Treatment: Drug: LOU064 (blinded); Drug: placebo

Detailed Description

This trial consists of 3 different periods:

1. the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 24 weeks. Total duration: approximately 32 weeks (10 site visits).
2. an optional "open-label extension (OLE) period" proposed to all participants who completed 24 weeks of treatment of the "core period" and all scheduled assessments planned at week 24 visit . Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 6 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 15 (depending on the CSU symptoms).
3. an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "OLE period". No treatment will be given. Duration: 3 years with 1 site visit and up to 4 phone call follow-up visits.

The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • CABA, Argentina, C1181ACH
    • Recruiting
    • Novartis Investigative Site
  • San Miguel de Tucumán, Argentina, 4000
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1414AIF
      • Recruiting
      • Novartis Investigative Site
    • CABA, Buenos Aires, Argentina, 1280
      • Recruiting
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1425BEN
      • Recruiting
      • Novartis Investigative Site
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Recruiting
      • Novartis Investigative Site
    • Rosario, Santa Fe Province, Argentina, S2000JKR
      • Recruiting
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Recruiting
      • Novartis Investigative Site
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Active, not recruiting
      • Novartis Investigative Site
• China
  • Beijing, China, 100050
    • Recruiting
    • Novartis Investigative Site
  • Beijing, China, 100069
    • Recruiting
    • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510091
      • Recruiting
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Recruiting
    • Novartis Investigative Site
  • Münster, Germany, 48149
    • Recruiting
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Recruiting
    • Novartis Investigative Site
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Recruiting
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Recruiting
    • Novartis Investigative Site
• Italy
  • Naples, Italy, 80138
    • Recruiting
    • Novartis Investigative Site
  • BA
    • Bari, BA, Italy, 70126
      • Recruiting
      • Novartis Investigative Site
  • FI
    • Florence, FI, Italy, 50139
      • Recruiting
      • Novartis Investigative Site
  • PR
    • Parma, PR, Italy, 43126
      • Recruiting
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Recruiting
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Recruiting
      • Novartis Investigative Site
  • TS
    • Trieste, TS, Italy, 34137
      • Recruiting
      • Novartis Investigative Site
• Japan
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 8078556
      • Recruiting
      • Novartis Investigative Site
  • Kumamoto
    • Kamimashi-gun, Kumamoto, Japan, 861-3106
      • Recruiting
      • Novartis Investigative Site
  • Osaka
    • Sakai, Osaka, Japan, 5938324
      • Recruiting
      • Novartis Investigative Site
  • Shimane
    • Izumo, Shimane, Japan, 6938501
      • Recruiting
      • Novartis Investigative Site
  • Tokyo
    • Itabashi-ku, Tokyo, Japan, 1738610
      • Recruiting
      • Novartis Investigative Site
• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Novartis Investigative Site
  • Overijssel
    • Deventer, Overijssel, Netherlands, 7416 SE
      • Recruiting
      • Novartis Investigative Site
• Poland
  • Lodz, Poland, 90-436
    • Recruiting
    • Novartis Investigative Site
  • Olsztyn, Poland, 10-045
    • Recruiting
    • Novartis Investigative Site
  • Warsaw, Poland, 02-962
    • Recruiting
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 229899
    • Recruiting
    • Novartis Investigative Site
  • Singapore, Singapore, 119074
    • Recruiting
    • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7925
    • Recruiting
    • Novartis Investigative Site
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0181
      • Recruiting
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Novartis Investigative Site
  • Valencia, Spain, 46014
    • Recruiting
    • Novartis Investigative Site
  • Barcelona
    • Esplugues, Barcelona, Spain, 08950
      • Recruiting
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Recruiting
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Recruiting
    • Novartis Investigative Site
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Recruiting
      • Novartis Investigative Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01330
    • Recruiting
    • Novartis Investigative Site
  • Fatih
    • Istanbul, Fatih, Turkey (Türkiye), 34093
      • Recruiting
      • Novartis Investigative Site
  • Sihhiye-Altindag
    • Ankara, Sihhiye-Altindag, Turkey (Türkiye), 06230
      • Recruiting
      • Novartis Investigative Site
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Novartis Investigative Site
  • Cambridgeshire
    • Peterborough, Cambridgeshire, United Kingdom, PE3 9GZ
      • Recruiting
      • Novartis Investigative Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Recruiting
      • Kern Research
      • Principal Investigator: Eric Boren
      • Contact: Wandy Noriega; Phone Number: 661-864-7710; Email: wandy.noriega@kernresearch.com
    • San Diego, California, United States, 92123
      • Recruiting
      • Allergy and Asthma Medical Group and Research Center
      • Principal Investigator: Bob Geng
      • Contact: Susan Smith; Phone Number: 858-268-2368; Email: susansmith@allergyandasthma.com
  • Florida
    • Miami, Florida, United States, 33156
      • Recruiting
      • Pediatric Dermatology of Miami at the Pediatric CoE
      • Principal Investigator: Mercedes E Gonzalez
      • Contact: Andrea Marin; Phone Number: 305-667-3152; Email: andrea@pediatricskinresearch.com
  • Idaho
    • Boise, Idaho, United States, 83706
      • Active, not recruiting
      • Treasure Valley Medical Research
  • Illinois
    • Glenview, Illinois, United States, 60077
      • Active, not recruiting
      • Endeavor Health
  • Kentucky
    • Owensboro, Kentucky, United States, 42301
      • Recruiting
      • Allergy and Asthma Specialist P S C
      • Principal Investigator: Lee Clore
      • Contact: Angela Haynes; Phone Number: 270-684-6144; Email: ahaynes@cloremd.com
  • Ohio
    • Toledo, Ohio, United States, 43617
      • Recruiting
      • Toledo Institute of Clinical Research
      • Principal Investigator: Syed Rehman
      • Contact: Abbas Zaidi; Phone Number: 419-843-8815; Email: abbas.zaidi@ohmiallergy.org
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Recruiting
      • Allergy Asthma and Clinical Research
      • Principal Investigator: Martha Tarpay
      • Contact: Meryem Assaoui; Phone Number: 405-752-0393; Email: meryem@mtarpay.com
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15241
      • Active, not recruiting
      • Allergy and Clinical Immunology Associates
  • Texas
    • San Antonio, Texas, United States, 78213
      • Recruiting
      • RFSA Dermatology
      • Principal Investigator: Lindsey Finklea
      • Contact: Jonathan Joseph; Email: jvjoseph007@gmail.com
  • Utah
    • Sandy City, Utah, United States, 84093
      • Completed
      • Allergy Associates of Utah
  • Washington
    • Seattle, Washington, United States, 98115
      • Withdrawn
      • Seattle Allergy and Asthma Rsch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male and female adolescent participants aged >= 12 to < 18 years of age at the time of signing the informed consent
• 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-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 according to local treatment guidelines
• 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)

Key Exclusion criteria:

• Previous use of remibrutinib or other BTK inhibitors
• Significant bleeding risk or coagulation disorders
• History of gastrointestinal bleeding
• Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited
• 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
• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
• 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 angioedema, 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

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: LOU064 (blinded); LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 6 cycles of 24 weeks.	Drug: LOU064 (blinded); LOU064 (blinded) active treatment; Other Names: remibrutinib
Placebo Comparator: Arm 2: LOU064 placebo (blinded); LOU064 placebo (blinded) taken orally b.i.d. for 24 weeks (randomized in a 2:1 ratio arm 1: arm 2)	Drug: placebo; matching active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in UAS7	The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement.	Baseline, week 12
Change fron baseline in ISS7	Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.	Baseline, Week 12
Change from baseline in HSS7	Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of remibrutinib	The maximum (peak) observed blood drug concentration after single dose administration	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Tmax of remibrutinib	The time to reach maximum (peak) blood drug concentration after single dose administration	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
AUClast of remibrutinib	The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time	At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
Absolute change from baseline in ISS7	Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement.	Baseline - Week 12
Absolute change from baseline in HSS7	Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement.	Baseline - Week 12
Achievement of UAS7 ≤ 6 (yes/no)	Disease activity control is defined as UAS7 ≤ 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.	Week 12 and over time
Achievement of UAS7 = 0 (yes/no)	Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42.	Week 12 and over time
Absolute change from baseline in CDLQI score	The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life).	Week 12
Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response	Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity.	baseline - Week 12
Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period	To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study.	28 weeks
Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period	To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study.	3 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2023
• Primary Completion (Estimated): November 6, 2026
• Study Completion (Estimated): March 30, 2032

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: December 23, 2022
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: BTK inhibitor; Chronic spontaneous urticaria; Urticaria activity score; Hives severity score; Itch severity score
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Urticaria; Skin Diseases, Vascular; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Chronic Urticaria; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; remibrutinib
• Other Study ID Numbers: CLOU064F12301; 2022-502159-78-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No